WO2005063235A1 - Anticancer therapy-aiding composition comprising polyphenol, and ascorbic acid or the derivatives - Google Patents
Anticancer therapy-aiding composition comprising polyphenol, and ascorbic acid or the derivatives Download PDFInfo
- Publication number
- WO2005063235A1 WO2005063235A1 PCT/KR2004/003478 KR2004003478W WO2005063235A1 WO 2005063235 A1 WO2005063235 A1 WO 2005063235A1 KR 2004003478 W KR2004003478 W KR 2004003478W WO 2005063235 A1 WO2005063235 A1 WO 2005063235A1
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- WO
- WIPO (PCT)
- Prior art keywords
- cisplatinum
- anticancer
- trail
- cells
- ascorbic acid
- Prior art date
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 88
- 239000000203 mixture Substances 0.000 title claims abstract description 87
- 150000008442 polyphenolic compounds Chemical class 0.000 title claims abstract description 59
- 235000013824 polyphenols Nutrition 0.000 title claims abstract description 59
- 235000010323 ascorbic acid Nutrition 0.000 title claims abstract description 48
- 229960005070 ascorbic acid Drugs 0.000 title claims abstract description 44
- 239000011668 ascorbic acid Substances 0.000 title claims abstract description 44
- 230000001093 anti-cancer Effects 0.000 title abstract description 20
- 238000011319 anticancer therapy Methods 0.000 claims abstract description 36
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 34
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 8
- 108700012411 TNFSF10 Proteins 0.000 claims description 73
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 8
- -1 epigaUocatechine Chemical compound 0.000 claims description 7
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims description 4
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims description 4
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims description 4
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 4
- 229960001285 quercetin Drugs 0.000 claims description 4
- 235000005875 quercetin Nutrition 0.000 claims description 4
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 claims description 3
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 3
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 3
- 235000010208 anthocyanin Nutrition 0.000 claims description 3
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- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Natural products C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 claims description 2
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 claims description 2
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 2
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- 229910052725 zinc Inorganic materials 0.000 claims description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims 1
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- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
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- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
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- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
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- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
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- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
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- DCYOBGZUOMKFPA-UHFFFAOYSA-N iron(2+);iron(3+);octadecacyanide Chemical compound [Fe+2].[Fe+2].[Fe+2].[Fe+3].[Fe+3].[Fe+3].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] DCYOBGZUOMKFPA-UHFFFAOYSA-N 0.000 description 1
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- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to a composition aiding anticancer therapy, comprising a polyphenol along with ascorbic acid or a derivative thereof
- Chemotherapy introduced for cancer treatment in 1940 is receiving lots of attention due to its advantage of being relatively easily applicable to cancer treatment regardless of the stage of cancer, and a variety of anticancer chemotherapeutic agents have been developed.
- platinum anticancer agents which are anticancer drugs that are most preferred among a broad range of currently used anticancer drugs, have been applied to treat a
- U.S. Pat. No. 5,391,568 discloses the inhibitory activity of a green tea polyphenol on lung tutnorigenesis.
- Korean Pat. Laid-open Publication No. 2002-0045417 discloses the anticancer effect of polyphenols extracted from green tea.
- Kemberling et al. reported that ⁇ igaUocatechin-3-gallate (EGCG) inhibits bladder tumor growth (Kemberling JK, Hampton JA, Keck RW et al.: Inhibition of bladder tumor growth by the green tea derivative ⁇ igallocatechin-3-gallate. J Urol. 170:773-6, 2003).
- Lung et al. reported that EGCG inhibits the proliferation and differentiation of leukemia cells
- composition for aiding anticancer therapy comprising comprises both a polyphenol and ascorbic acid or a derivative thereof, the composition being capable of remarkably increasing anticancer effects of
- the present composition for aiding anticancer therapy has an effect of enhancing the inhibitory effect of an anticancer agent against the activity of cancer cells.
- the present invention provides a composition for aiding anticancer therapy, comprising both a polyphenol and ascorbic acid or a derivative thereof.
- the present composition for aiding anticancer therapy comprises 50.0-99.9 parts by
- the polyphenol contained in the present composition for aiding anticancer therapy may be one or more selected from among epicatechin, epicatechin gallate, epigaUocatechine, epigallocatechin gallate, anthocyanin, resveratrol and quercetin.
- the polyphenol contained in the present composition for aiding anticancer therapy may be one or more selected from among ⁇ icatechin, epicatechin gallate, epigaUocatechine and epigallocatechin gallate extracted from green tea, anthocyanin,
- the ascorbic acid or derivative thereof contained in the present composition for aiding anticancer therapy may be one or more selected from among ascorbic acid, ascorbyl palmitate, calcium ascorbates, magnesium ascorbates and zinc ascorbates.
- the present composition for aiding anticancer therapy increases the cytotoxic effect
- the present composition for aiding anticancer therapy improves the cytotoxic effect of a platinum anticancer agent or tumor necrosis factor-related apoptosis inducing ligand (TRAIL) against cancer cells.
- Platinum anticancer agents which are drugs containing platinum molecules in their chemical structure, bind to DNA and interfere with DNA replication in cancer cells, thus
- TRAIL is known to be cytotoxic against cancer cells by inducing apoptosis. Recently, many studies have been focused on the anticancer activity of TRAIL.
- an anticancer agent such as cisplatinum or TRAIL
- the present composition for aiding anticancer therapy enhances the toxicity of the anticancer agent against cancer cells 2-4 times. That is, the present composition for aiding anticancer therapy maintains the anticancer effect of an anticancer agent used together even in very low concentrations of the anticancer agent, thereby increasing efficiency of the anticancer agent as weE as preventing
- the green tea polyphenol, contained in the present composition for aiding anticancer therapy may be prepared by any method capable of extracting, isolating and purifying the polyphenol from green tea
- a method of preparing a green tea extract disclosed inKoreanPat. Registration Publication No. 10-377313, maybe used. In the above method, 5-20 parts by weight of water or alcohol are added to 1 part by
- the above method may further include removing caffeine or increasing concentrations of polyphenols.
- the ascorbic acid contained in the present composition for aiding anticancer therapy may be any commercially available product.
- the green tea polyphenol and ascorbic acid, as prepared above, are mixed in amounts of 50-95 parts by weight and 5-50 parts by weight, respectively, to provide the present composition.
- the present composition may include other effective components having functions identical or similar to those of the above components.
- present composition may further include other effective components
- the present composition may include one or more pharmaceutically acceptable
- the pharmaceutically acceptable carrier may be selected from among physiological
- the present composition may include other common additives, such as an antioxidant, a buffer and a bacteriostatic.
- the present composition may further include a diluting agent, a dispersing agent, a surfactant, a binder and a lubricant so as to be formulated as injectable preparations such as aqueous solutions, suspensions and emulsions, pills, capsules, granules or tablets.
- the present composition may be preferably formulated according to diseases to be treated or its components using suitable methods in the art or methods disclosed in Remington's Pharmaceutical Science (recent version), Mack Publishing Company, Easton PA.
- the pharmaceutical composition of the present invention is preferably provided in
- the dosage or intake of the pharmaceutical composition of the present invention may be suitably selected within the range of about several hundred mg to several g as an adult single dose for powders, and within the range of about several ml to several hundred ml as an adult single dose for solutions.
- the dosage or intake may vary depending on various factors
- compositions including the types and contents of effective components and other components contained in a composition, formulation types, the patient's age, weight, general health state, gender and diet,
- the pharmaceutical composition of the present invention does not exhibit adverse effects when administered to the body because it is extracted from native sources.
- the present composition for aiding anticancer therapy may be useful as an adjuvant in anticancer therapy using platinum-based anticancer agents with no risk of causing adverse effects.
- EXAMPLE 1 Preparation of the composition of the present invention To prepare the present composition, green tea polyphenol powder and ascorbic acid were prepared as follows. The green tea polyphenol powder contained in the present composition was extracted, isolated and purified according to a method of preparing a green tea extract, disclosed in Korean Pat. Registration Publication No. 10-377313.
- the extract was analyzed as follows.
- the green tea extract was subjected to HPLC (high performance liquid chromatography) for quantitative analysis of each polyphenol and caffeine, and a spectrophotometric redox assay using Prussian Blue reaction for quantitative analysis of whole polyphenols.
- HPLC high performance liquid chromatography
- Prussian Blue reaction quantitative analysis of whole polyphenols.
- Ascorbic acid Catalog No. A5960 contained in the present composition and a composition added to a comparative group 1 , below, was purchased from Sigma Chemical Co.
- EXAMPLE 2 The enhancing effect of the present composition on cytotoxicity of cisplatinum in cervical carcinoma cells The enhancing effect of the present composition on cytotoxicity of cisplatinum was assessed in cervical carcinoma cells.
- test group treated with both cisplatinum and the present composition.
- HeLa cells were plated onto a 96-well plate at a density of 2x 10 5 cells per well and cultured for one day.
- PBS containing cisplatinum (Sigma Chemical Co., USA) was added to wells of the control group.
- PBS containing 20 ⁇ g/ml of ascorbic acid, prepared in Example 1 was added to wells of the comparative group 1.
- Cisplatinum was added to wells of each group in various concentrations of 0, 50,
- the cells of each group were then cultured for 24 hrs in a CO 2 incubator.
- the viability of the cell was measured by a 3-(4,5-dimemylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
- the percentage of cell viability was calculated by multiplying the ratio absorbance of the test group versus the control group by 100. Each value represents the mean value of three independent experiments. The results are given in Table 1 , below.
- cell viability started to decrease at 100 ⁇ g/ml of cisplatinum and decreased to 59%, 22%, 12%, 11%, 10% and 6% at 200, 400, 600, 800 and 1000 ⁇ g/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
- cell viability started to decrease at 100 ⁇ g/ml of cisplatinum and decreased to 51%, 17%, 11%, 11%, 8% and 5% at 200, 400, 600, 800 and 1000 ⁇ g/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
- EXAMPLE 3 The enhancing effect of the present composition on cytotoxicity of
- cell viability started to decrease at 400 ⁇ g/ml of cisplatinum and decreased to 57%, 21%, 15% and 13% at 400, 600, 800 and 1000 ⁇ g/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
- cell viability started to decrease at 200 ⁇ g/ml of cisplatinum and decreased to 42%, 15%, 10%, 13% and 8% at 200, 400, 600, 800 and 1000 ⁇ g/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
- the present composition containing both green tea polyphenol powder and ascorbic acid, decreased cell
- EXAMPLE 4 The enhancing effect of the present composition on cytotoxicity of
- test group A549 cells were plated onto a 96-well plate at a
- TRAIL 100 and 200 ⁇ g/ml, respectively, was added to wells of the test group.
- TRAIL was added to wells of each group in various concentrations of 0, 10, 20, 40,
- TRAIL should be used in much higher concentrations so as to achieve significant anticancer efficacy when TRAIL is administered alone or in combination with ascorbic acid.
- TRAIL should be used in much higher concentrations so as to achieve significant anticancer efficacy when TRAIL is administered alone or in combination with ascorbic acid.
- cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 49%, 12%, 9%, 10%, 12% and 8% at 20, 40, 60, 80, 100 and 200 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
- cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 45%, 16%, 13%, 8%, 11% and 10% at 20, 40, 60, 80, 100 and 200 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL. That is, a decrease in cell viability was found at 40 ng/ml or higher of TRAIL in the
- the present composition containing both green tea polyphenol powder and ascorbic acid, showed decreased cell viability even at 20 ng/ml of TRAIL.
- This suppressive effect of the present composition on cellular activity was 2 times higher than when cells were treated with green tea polyphenol powder only.
- This enhancing effect of the present composition on anticancer activity of TRAIL was much higher than that of green tea polyphenol powder or ascorbic acid used alone as an
- EXAMPLE 5 The enhancing effect of the present composition on cytotoxicity of TRAIL in cervical carcinoma cells The enhancing effect of the present composition on cytotoxicity of TRAIL was assessed in cervical carcinoma cells.
- cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 35%, 14%, 10%, 6% and 5% at 20, 40, 60, 80 and 100 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
- the present composition for aiding anticancer therapy maintains the anticancer effect of an anticancer agent used together even in very low concentrations of the anticancer agent, thereby increasing the efficiency of the anticancer agent as well as preventing adverse effects caused by abuse of the anticancer agent.
- the present composition for aiding anticancer therapy is useful as an adjuvant in anticancer therapy for squamous cell carcinomas and adenocarcinomas using an anticancer drug.
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Abstract
Disclosed is a composition for aiding anticancer therapy, comprising 'both a polyphenol and ascorbic acid or a derivative thereof The composition for aiding anticancer therapy includes 50.0-99.9 parts by weight of a polyphenol and 0.1-50.0 parts by weight of ascorbic acid or a derivative thereof, and is administered in combination with a platinum anticancer agent or TRAIL. The composition for aiding anticancer therapy enhances the inhibitory effect of an anticancer agent against the activity of cancer cells, and maintains the anticancer effect of an anticancer agent used together even at very low concentrations of the anticancer agent.
Description
ANTICANCER THERAPY-AIDING COMPOSITION COMPRISING POLYPHENOL, AND ASCORBIC ACID OR THE DERIVATIVES
Technical Field The present invention relates to a composition aiding anticancer therapy, comprising a polyphenol along with ascorbic acid or a derivative thereof
Background Art Chemotherapy introduced for cancer treatment in 1940 is receiving lots of attention due to its advantage of being relatively easily applicable to cancer treatment regardless of the stage of cancer, and a variety of anticancer chemotherapeutic agents have been developed.
However, many currently available chemotlierapeutic agents are limited in their aciministration owing to their adverse effects and the emergence of resistance in cancer cells. For this reason, cancer chemotherapy is carried out essentially in combination with an adjuvant treatment. Widely used adjuvant treatments include combination therapy with anticancer
agents, high-dose chemotherapy and radiotherapy. However, since these therapies increase adverse effects even though they improve the effects of chemotherapeutic agents, they are
difficult to apply clinically. For example, platinum anticancer agents, which are anticancer drugs that are most preferred among a broad range of currently used anticancer drugs, have been applied to treat a
wide range of cancer. However, they have a problem in that several types of cancer cells have developed resistance to platinum anticancer drugs, leading to an increase in dosage or the
requirement for replacing them with another anticancer drug. Thus, it is very important to develop agents capable of enhancing the anticancer activity of chemotherapeutic agents along
with the development of anticancer agents. Polyphenols are known to exert direct effects on prevention of cancer incidence and
treatment of cancer. For example, U.S. Pat. No. 5,391,568 discloses the inhibitory activity of a green tea polyphenol on lung tutnorigenesis. Korean Pat. Laid-open Publication No. 2002-0045417 discloses the anticancer effect of polyphenols extracted from green tea In addition, Kemberling et al. reported that φigaUocatechin-3-gallate (EGCG) inhibits bladder tumor growth (Kemberling JK, Hampton JA, Keck RW et al.: Inhibition of bladder tumor growth by the green tea derivative φigallocatechin-3-gallate. J Urol. 170:773-6, 2003). Lung et al. reported that EGCG inhibits the proliferation and differentiation of leukemia cells
(Lung HL, Ip WK, Wong CK et al.: Anti-proliferative and differentiation-inducing activities of the green tea catechin φigaUocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line. Life Sci. 72:257-68. 2002). Fujiki et al. reported that green tea has preventive
and therapeutic efficacy against cancer (Fujiki H, Suganuma M, ϊmai K, Nakachi K: Green tea: cancer preventive beverage and/or drug. Cancer Lett. 188:9-13.2002). In addition, ascorbic acid, which is a vitamin having antioxidant effects, is reported to
exhibit anticancer effects. However, there is no report of an anticancer drug having remarkably enhanced anticancer effects when administered along with a composition comprising both a polyphenol
and ascorbic acid. In this regard, the present inventors found that, when a composition comprising both
a polyphenol and ascorbic acid is used as an adjuvant in anticancer therapy, the efficiency of anticancer therapy is remarkably enhanced in comparison with the individual use of the active
components, thus leading to the present invention.
Disclosure of the Invention Technical Solution It is therefore an object of the present invention to provide a composition for aiding anticancer therapy, comprising comprises both a polyphenol and ascorbic acid or a derivative thereof, the composition being capable of remarkably increasing anticancer effects of
conventional anticancer agents in comparison with the individual use of each component.
Advantageous Effects The present composition for aiding anticancer therapy has an effect of enhancing the inhibitory effect of an anticancer agent against the activity of cancer cells.
Best Mode for Carrying Out the Invention The present invention provides a composition for aiding anticancer therapy, comprising both a polyphenol and ascorbic acid or a derivative thereof. The present composition for aiding anticancer therapy comprises 50.0-99.9 parts by
weight of a polyphenol and 0.1-50.0 parts by weight of ascorbic acid, and preferably 70-95 parts by weight of apolyphenol and 2-30 parts by weight of ascorbic acid. The polyphenol contained in the present composition for aiding anticancer therapy may be one or more selected from among epicatechin, epicatechin gallate, epigaUocatechine, epigallocatechin gallate, anthocyanin, resveratrol and quercetin.
In detail, the polyphenol contained in the present composition for aiding anticancer therapy may be one or more selected from among φicatechin, epicatechin gallate, epigaUocatechine and epigallocatechin gallate extracted from green tea, anthocyanin,
resveratrol and quercetin extracted from grapes, and quercetin extracted from onions.
The ascorbic acid or derivative thereof contained in the present composition for aiding anticancer therapy may be one or more selected from among ascorbic acid, ascorbyl palmitate, calcium ascorbates, magnesium ascorbates and zinc ascorbates. The present composition for aiding anticancer therapy increases the cytotoxic effect
of an anticancer agent against cancer cells when administered in combination with the anticancer agent. In detail, the present composition for aiding anticancer therapy improves the cytotoxic effect of a platinum anticancer agent or tumor necrosis factor-related apoptosis inducing ligand (TRAIL) against cancer cells. Platinum anticancer agents, which are drugs containing platinum molecules in their chemical structure, bind to DNA and interfere with DNA replication in cancer cells, thus
displaying cytotoxic effects against cancer cells. Representative examples include cisplatinum and caώoplatinum. TRAIL is known to be cytotoxic against cancer cells by inducing apoptosis. Recently, many studies have been focused on the anticancer activity of TRAIL. When used in combination with an anticancer agent such as cisplatinum or TRAIL, the present composition for aiding anticancer therapy enhances the toxicity of the anticancer agent against cancer cells 2-4 times. That is, the present composition for aiding anticancer therapy maintains the anticancer effect of an anticancer agent used together even in very low concentrations of the anticancer agent, thereby increasing efficiency of the anticancer agent as weE as preventing
adverse effects caused by abuse of the anticancer agent. The aforementioned effects of the present composition are much higher than
expected effects when the components of the present composition are individually used.
Hereinafter, a method of preparing the present composition for aiding anticancer therapy will be described.
The green tea polyphenol, contained in the present composition for aiding anticancer therapy, may be prepared by any method capable of extracting, isolating and purifying the polyphenol from green tea For example, a method of preparing a green tea extract, disclosed inKoreanPat. Registration Publication No. 10-377313, maybe used. In the above method, 5-20 parts by weight of water or alcohol are added to 1 part by
weight of hot air-dried green tea leaf powder. After agitation for 15 min to 24 hrs at 1-100°C, the green tea leaf powder is removed, and the resulting solution is cooled to remove precipitates. The thus-obtained extract is again heated, cooled to remove precipitates, and dried to give a final green tea extract. The drying is preferably carried out by spray-drying, and the green tea extract is preferably in a powder form. The above method may further include removing caffeine or increasing concentrations of polyphenols. The ascorbic acid contained in the present composition for aiding anticancer therapy may be any commercially available product.
The green tea polyphenol and ascorbic acid, as prepared above, are mixed in amounts of 50-95 parts by weight and 5-50 parts by weight, respectively, to provide the present composition. In addition to the above components, the present composition may include other effective components having functions identical or similar to those of the above components.
In addition, the present composition may further include other effective components
having functions different from those of the above components. The present composition may include one or more pharmaceutically acceptable
carriers as well as the aforementioned effective components to be provided as a pharmaceutical
composition, and maybe formulated into a pharmaceutical preparation. The pharmaceutically acceptable carrier may be selected from among physiological
saline, sterile water, Ringer's solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof. If desired, the present composition may include other common additives, such as an antioxidant, a buffer and a bacteriostatic. Also, the present composition may further include a diluting agent, a dispersing agent, a surfactant, a binder and a lubricant so as to be formulated as injectable preparations such as aqueous solutions, suspensions and emulsions, pills, capsules, granules or tablets. Moreover, the present composition may be preferably formulated according to diseases to be treated or its components using suitable methods in the art or methods disclosed in Remington's Pharmaceutical Science (recent version), Mack Publishing Company, Easton PA. The pharmaceutical composition of the present invention is preferably provided in
the form of solutions, powders, capsules, tablets and syrups, and may be also provided as powders, granules, coated tablets, decoctions, extracts, suppositories, juices, suspensions, emulsions, preparations topically applicable on the skin, or sustained release preparations of active compounds. The dosage or intake of the pharmaceutical composition of the present invention may be suitably selected within the range of about several hundred mg to several g as an adult single dose for powders, and within the range of about several ml to several hundred ml as an adult single dose for solutions. The dosage or intake may vary depending on various factors
including the types and contents of effective components and other components contained in a composition, formulation types, the patient's age, weight, general health state, gender and diet,
administration time, administration routes and excretion rates of the composition, treatment
duration, and other drags used.
The pharmaceutical composition of the present invention does not exhibit adverse effects when administered to the body because it is extracted from native sources.
Thus, the present composition for aiding anticancer therapy may be useful as an adjuvant in anticancer therapy using platinum-based anticancer agents with no risk of causing adverse effects.
Mode for the Invention A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as the limit of the present invention.
EXAMPLE 1: Preparation of the composition of the present invention To prepare the present composition, green tea polyphenol powder and ascorbic acid were prepared as follows. The green tea polyphenol powder contained in the present composition was extracted, isolated and purified according to a method of preparing a green tea extract, disclosed in Korean Pat. Registration Publication No. 10-377313.
In order to determine whether a purified extract has high content of green tea • polyphenols, the extract was analyzed as follows. The green tea extract was subjected to HPLC (high performance liquid chromatography) for quantitative analysis of each polyphenol and caffeine, and a spectrophotometric redox assay using Prussian Blue reaction for quantitative analysis of whole polyphenols. As a result, the green tea polyphenol powder obtained in this Example was found to contain more than 83% polyphenols.
Ascorbic acid (Catalog No. A5960) contained in the present composition and a composition added to a comparative group 1 , below, was purchased from Sigma Chemical Co.
(USA). 900 g of the green tea polyphenol powder and 100 g of ascorbic acid, prepared as
described above, were mixed to provide the present composition.
EXAMPLE 2: The enhancing effect of the present composition on cytotoxicity of cisplatinum in cervical carcinoma cells The enhancing effect of the present composition on cytotoxicity of cisplatinum was assessed in cervical carcinoma cells.
1) Cell culture Cervical carcinoma HeLa cells (squamous cell carcinoma), which were obtained from the Korean Cell Line Bank, were used in this Example. The cells were cultured in RPMI 1640 (Gibco BRL) supplemented with 10% fetal bovine serum, streptomycin (100
U/ml) and penicillin (100 U/ml) in a CO incubator at 37°C.
2) The effect of the present composition on cytotoxicity of cisplatinum in cervical carcinoma cells Using HeLa cells cultured as described above, six groups were prepared, which consisted of a control group treated with cisplatinum only, a treatment group (comparative
group 1) treated with both cisplatinum and ascorbic acid, another treatment group (comparative group 2) treated with both cisplatinum and green tea polyphenols, and a further treatment
group (test group) treated with both cisplatinum and the present composition. To prepare each of the groups, HeLa cells were plated onto a 96-well plate at a
density of 2x 105 cells per well and cultured for one day. PBS containing cisplatinum (Sigma Chemical Co., USA) was added to wells of the control group.
PBS containing 20 μg/ml of ascorbic acid, prepared in Example 1 was added to wells of the comparative group 1. PBS containing green tea polyphenols, prepared in Example 1, in concentrations of
100 and 200 μg ml, respectively, was added to wells of the comparative group 2. PBS containing green tea polyphenols, prepared in Example 1, in concentrations of
100 and 200 μg/ml, respectively, was added to wells of the test group. Cisplatinum was added to wells of each group in various concentrations of 0, 50,
100, 200, 400, 600, 800 and 1000 μg/ml. The cells of each group were then cultured for 24 hrs in a CO2 incubator. The viability of the cell was measured by a 3-(4,5-dimemylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The percentage of cell viability was calculated by multiplying the ratio absorbance of the test group versus the control group by 100. Each value represents the mean value of three independent experiments. The results are given in Table 1 , below.
TABLE 1
started to decrease at 400 μg/ml of cisplatinum and decreased to 14% at 600 μg/ml of cisplatinum compared to when not treated with cisplatinum. These results were consistent with the known cytotoxic effects of ciφlatinum. Similarly, when HeLa cells were treated with cisplatinum along with ascorbic acid,
the viability of the cells started to decrease at 400 μg/ml of cisplatinum and decreased to below
14% at 600 μg/ml of cisplatinum. These results indicate that the use of cisplatinum in combination with ascorbic acid rarely enhances the anticancer effect of cisplatinum.
When HeLa cells were treated with cisplatinum along with 100 μg/ml of green tea polyphenol powder, cell viability started to decrease at 200 μg/ml of cisplatinum and decreased to 68%, 17%, 11%, 13% and 14% at 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to control cells not treated with cisplatinum. When cells were treated with cisplatinum along with 200 μg/ml of green tea polyphenol powder, cell viability started to decrease at 100 μg/ml of cisplatinum and decreased
to 76%, 35%, 11%, 12%, 8% and 11% at 100, 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
On the other hand, when cells were treated with cisplatinum along with 100 μg/ml of
the present composition, cell viability started to decrease at 100 μg/ml of cisplatinum and
decreased to 59%, 22%, 12%, 11%, 10% and 6% at 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
When cells were treated with cisplatinum along with 200 μg/ml of the present
composition, cell viability started to decrease at 100 μg/ml of cisplatinum and decreased to 51%, 17%, 11%, 11%, 8% and 5% at 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
That is, a decrease in cell viability was found at 400 μg/ml or higher of cisplatinum in the control group treated with cisplatinum only, and at 200 μg/ml or higher of cisplatinum in the group treated along with green tea polyphenol powder. In contrast, the present composition, containing both green tea polyphenol powder and ascorbic acid, decreased cell
viability even at 100 μg/ml of cisplatinum. This suppressive effect of the present composition on cellular activity was 2-4 times higher than when cells were treated with cisplatinum or green
tea polyphenol powder only. This enhancing effect of the present composition on anticancer activity of cisplatinum was much higher than that of green tea polyphenol powder or ascorbic acid used
alone as an adjuvant in anticancer therapy. These results indicate that the present composition enhances the cytotoxicity of cisplatinum against cancer cells with much higher efficiency than singly added green tea polyphenol powder or ascorbic acid.
EXAMPLE 3: The enhancing effect of the present composition on cytotoxicity of
cisplatinum in lung carcinoma cells The enhancing effect of the present composition on the cytotoxicity of cisplatinum
was assessed in lung carcinoma cells.
1) Cell culture A549 lung adenocarcinoma cells, which were obtained from the Korean Cell Line Bank, were used in this Example. The cells were cultured under the same conditions as in the
1) of Example 2.
2) The effect of the present composition on cytotoxicity of cisplatinum in lung carcinoma cells Cells were treated with the present invention according to the same methods as in the 2) of Example 2. The results are given in Table 2, below.
TABLE 2
As shown in Table 2, in the control group treated with cisplatinum only, cell viability
started to decrease at 800 μg/ml of cisplatinum and decreased to 51% and 15% at 800 and
1000 μg/ml of cisplatinum, respectively, compared to when not treated with cisplatinum.
These results were consistent with the known cytotoxic effects of cisplatinum. Similarly, when cells were treated with cisplatinum along with ascorbic acid, the
viability of the cells started to decrease at 800 μg/ml of cisplatinum and decreased to 68% and
19% at 800 and 1000 μghil of cisplatinum, respectively. These results indicate that the use of cisplatinum in combination with ascorbic acid rarely enhances the anticancer effect of cisplatinum.
When cells were treated with cisplatinum along with 100 μg/ml of green tea polyphenol powder, cell viability started to decrease at 400 μg/ml of cisplatinum and decreased to 57%, 21%, 15% and 13% at 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
When cells were treated with cisplatinum along with 200 μg/ml of green tea polyphenol powder, cell viability started to decrease at 200 μg/ml of cisplatinum and decreased to 75%, 22%, 16%, 14% and 15% at 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum. On the other hand, when cells were treated with cisplatinum along with 100 μg/ml of the present composition, cell viability started to decrease at 200 μg/ml of cisplatinum and decreased to 42%, 15%, 10%, 13% and 8% at 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
When cells were treated with cisplatinum along with 200 μg/ml of the present composition, cell viability started to decrease at 200 μg/ml of cisplatinum and decreased to
47%, 14%, 9%, 7% and 9% at 200, 400, 600, 800 and 1000 μg/ml of cisplatinum, respectively, compared to the control cells not treated with cisplatinum.
That is, a decrease in cell viability was found at 400 μg/ml or higher of cisplatinum in
the control group treated with cisplatinum only, and at 200 μ /ml or higher of cisplatinum in
the group treated along with green tea polyphenol powder. In contrast, the present composition, containing both green tea polyphenol powder and ascorbic acid, decreased cell
viability even at 100 μg/ml of cisplatinum. This suppressive effect of the present composition on cellular activity was 2-4 times higher than when cells were treated with cisplatinum or green tea polyphenol powder only. This enhancing effect of the present composition on anticancer activity of cisplatinum was much higher than that of green tea polyphenol powder or ascorbic acid used
alone as an adjuvant in anticancer therapy. These results indicate that the present composition enhances the cytotoxicity of cisplatinum against cancer cells with much higher efficiency than individually added green tea
polyphenol powder or ascorbic acid.
EXAMPLE 4: The enhancing effect of the present composition on cytotoxicity of
TRAIL in lung carcinoma cells The enhancing effect of the present composition on cytotoxicity of TRAIL was
assessed in lung carcinoma cells.
1) Cell culture A549 lung adenocarcinoma cells, which were obtained from the Korean Cell Line Bank, were used in this Example. The cells were cultured under the same conditions as in the
1) of Example 2.
2) The effect of the present composition on cytotoxicity of TRAIL in lung carcinoma cells Using A549 cells cultured as described above, six groups were prepared, which
consisted of a control group treated with TRAIL only, a treatment group treated with both
TRAIL and ascorbic acid (comparative group 1), another treatment group treated with both TRAIL and green tea polyphenols (comparative group 2), and a further treatment group treated
with both TRAIL and tiie present composition (test group). To prepare each of the groups, A549 cells were plated onto a 96-well plate at a
density of 2x 105 cells per well and cultured for one day. PBS containing TRAIL (Sigma Chemical Co., USA) was added to wells of the
control group. PBS containing 20 μg/ml of ascorbic acid, prepared in Example 1, was added to wells of the comparative group 1. PBS containing green tea polyphenols, prepared in Example 1, in concentrations of
100 and 200 μg/ml, respectively, was added to wells of the comparative group 2. PBS containing green tea polyphenols, prepared in Example 1, in concentrations of
100 and 200 μg/ml, respectively, was added to wells of the test group. TRAIL was added to wells of each group in various concentrations of 0, 10, 20, 40,
60, 80, 100 and200ng/ml. The cells of each group were then cultured for 24 hrs in a CO2 incubator. The viability of the cell was measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The percentage of cell viability was calculated by multiplying the ratio absorbance of the test group versus the control group by 100. Each value represents the mean value of three independent experiments. The results are given in Table 3, below.
TABLE 3
not decrease even at 200 ng/ml of TRAIL. Similarly, when cells were treated with TRAIL along with ascorbic acid, the viability of the cells did not decrease even at 200 ng/ml of TRAIL. These results indicate that TRAIL should be used in much higher concentrations so as to achieve significant anticancer efficacy when TRAIL is administered alone or in combination with ascorbic acid. When cells were treated with TRAIL along with 100 μg/ml of green tea polyphenol powder, cell viability started to decrease at 40 ng/ml of TRAIL and decreased to 48%, 11%,
10%, 9% and 10% at 40, 60, 80, 100 and 200 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
When cells were treated with TRAIL along with 200 μg/ml of green tea polyphenol powder, cell viability started to decrease at 40 ng/ml of TRAIL and decreased to 44%, 12%,
7%, 9% and 10% at 40, 60, 80, 100 and 200 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
On the other hand, when cells were treated with TRAIL along with 100 μg/ml of the present composition, cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 49%, 12%, 9%, 10%, 12% and 8% at 20, 40, 60, 80, 100 and 200 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
When cells were treated with TRAIL along with 200 μg ml of the present composition, cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 45%, 16%, 13%, 8%, 11% and 10% at 20, 40, 60, 80, 100 and 200 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL. That is, a decrease in cell viability was found at 40 ng/ml or higher of TRAIL in the
group treated along with 100 μg/ml of green tea polyphenol powder, hi contrast, the present composition, containing both green tea polyphenol powder and ascorbic acid, showed decreased cell viability even at 20 ng/ml of TRAIL. This suppressive effect of the present composition on cellular activity was 2 times higher than when cells were treated with green tea polyphenol powder only. This enhancing effect of the present composition on anticancer activity of TRAIL was much higher than that of green tea polyphenol powder or ascorbic acid used alone as an
adjuvant in anticancer therapy. These results indicate that the present composition enhances the cytotoxicity of
TRAIL against cancer cells with much higher efficiency than individually added green tea
polyphenol powder or ascorbic acid.
EXAMPLE 5: The enhancing effect of the present composition on cytotoxicity of TRAIL in cervical carcinoma cells The enhancing effect of the present composition on cytotoxicity of TRAIL was assessed in cervical carcinoma cells.
1) Cell culture Cervical carcinoma SiHa cells, which were obtained from the Korean Cell Line Bank, were used in this Example. The cells were cultured under the same conditions as in the
1) of Example 4.
2) The effect of the present composition on cytotoxicity of TRAIL in cervical carcinoma
cells Cells were treated with the present invention according to the same methods as in the 2) of Example 4. The results are given in Table 4, below.
TABLE 4
80 and 100 ng/ml of TRAIL, respectively, compared to when not treated with TRAIL. These results were consistent with the known cytotoxic effects of TRAIL. Similarly, when cells were treated with TRAIL along with ascorbic acid, the viability of the cells started to decrease at 40 ng/ml of TRAIL and decreased to 42%, 18%, 9% and 8% at 40, 60, 80 and 100 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL. These results indicate that the use of TRAIL in combination with ascorbic acid rarely
enhances the anticancer effect of TRAIL.
When cells were treated with TRAIL along with 100 μg/ml of green tea polyphenol powder, cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 47%, 14%, 11%, 7% and 8% at 20, 40, 60, 80 and 100 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
When cells were treated with TRAIL along with 200 μg/ml of green tea polyphenol powder, cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 41%, 12%, 9%, 8% and 7% at 20, 40, 60, 80 and 100 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL. On the other hand, when cells were treated with TRAIL along with 100 μg/ml of the present composition, cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 32%, 11%, 8%, 8% and 7% at 20, 40, 60, 80 and 100 ng/ml of TRAIL, respectively,
compared to the control cells not treated with TRAIL.
When cells were treated with TRAIL along with 200 μg/ml of the present
composition, cell viability started to decrease at 20 ng/ml of TRAIL and decreased to 35%, 14%, 10%, 6% and 5% at 20, 40, 60, 80 and 100 ng/ml of TRAIL, respectively, compared to the control cells not treated with TRAIL.
These results indicate that the present composition enhances the cytotoxicity of TRAIL against cancer cells with high efficiency.
Industrial Applicability As described hereinbefore, the present composition for aiding anticancer therapy maintains the anticancer effect of an anticancer agent used together even in very low concentrations of the anticancer agent, thereby increasing the efficiency of the anticancer agent as well as preventing adverse effects caused by abuse of the anticancer agent.
Therefore, the present composition for aiding anticancer therapy is useful as an adjuvant in anticancer therapy for squamous cell carcinomas and adenocarcinomas using an anticancer drug.
Claims
Claims 1. A composition for aiding anticancer therapy, comprising both a polyphenol and ascorbic acid or a derivative thereof.
2. The composition for aiding anticancer therapy according to claim 1, wherein the polyphenol is contained in an amount of 50.0-99.9 parts by weight, and the ascorbic acid or derivative thereof is contained in an amount of 0.1-50.0 parts by weight.
3. The composition for aiding anticancer therapy according to claim 2, wherein the polyphenol is one or more selected from among epicatechin, φicatechin gallate, epigaUocatechine, epigallocatechin gallate, anthocyanin, resveratrol and quercetin.
4. The composition for aiding anticancer therapy according to claim 3, wherein the ascorbic acid or derivative thereof is one or more selected from among ascorbic acid, ascorbyl palmitate, calcium ascorbates, magnesium ascorbates and zinc ascorbates.
5. The composition for aiding anticancer therapy according to claim 4, which is used in combination with a platinum anticancer agent.
6. The composition for aiding anticancer therapy according to claim 4, which is used
in combination with an anticancer agent, tumor necrosis factor-related apoptosis inducing ligand (TRAIL).
7. The composition for aiding anticancer therapy according to claim 5 or 6, which is used in anticancer therapy for a squamous cell carcinoma or an adenocarcinoma
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020030099850A KR20050070385A (en) | 2003-12-30 | 2003-12-30 | Anticancer therapy - aiding composition comprising polyphenol, and ascorbic acid or the derivatives |
| KR10-2003-0099850 | 2003-12-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2005063235A1 true WO2005063235A1 (en) | 2005-07-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2004/003478 WO2005063235A1 (en) | 2003-12-30 | 2004-12-28 | Anticancer therapy-aiding composition comprising polyphenol, and ascorbic acid or the derivatives |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR20050070385A (en) |
| WO (1) | WO2005063235A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011026219A1 (en) * | 2009-09-01 | 2011-03-10 | Lu qing-bin | Combination therapy for cancer comprising a platinum -based antineoplastic agent and a biocompatible electron donor |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003057211A1 (en) * | 2002-01-08 | 2003-07-17 | Matthias Rath | Composition inhibiting matrix-metallproteinases for the treatmentof neoplastic diseases. |
-
2003
- 2003-12-30 KR KR1020030099850A patent/KR20050070385A/en not_active Ceased
-
2004
- 2004-12-28 WO PCT/KR2004/003478 patent/WO2005063235A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003057211A1 (en) * | 2002-01-08 | 2003-07-17 | Matthias Rath | Composition inhibiting matrix-metallproteinases for the treatmentof neoplastic diseases. |
Non-Patent Citations (5)
| Title |
|---|
| CHEN ET AL: "Combination with water-soluble antioxidants increases the anticancer activity of quercetin in human leukemia cells", PHARMAZIE, vol. 59, no. 11, November 2004 (2004-11-01), pages 859 - 863 * |
| ISHINO ET AL: "Effect of anticancer drugs, metals and antioxidants on cytotoxic activity of epigallocatechin gallate", ANTICANCER RES., vol. 19, no. 5B, September 1999 (1999-09-01) - October 1999 (1999-10-01), pages 4343 - 4348 * |
| JIANG ET AL: "Combination effect of lignan F and natural products", ANTICANCER RES., vol. 21, no. 2A, March 2001 (2001-03-01) - April 2001 (2001-04-01), pages 965 - 970 * |
| KANDASWAMI ET AL: "Ascorbic acid-enhanced antiproleferative effect of flavonoids on squamous cell carcinoma in vitro", ANTICANCER DRUGS, vol. 4, no. 1, February 1993 (1993-02-01), pages 91 - 96 * |
| WEI ET AL: "Inhibition of liver cancer cell proleferation and migration by a combination of(-)- epigallocatechin-3-gallate and ascorbic acid", J. CHEMOTHER., vol. 15, no. 6, December 2003 (2003-12-01), pages 591 - 595 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011026219A1 (en) * | 2009-09-01 | 2011-03-10 | Lu qing-bin | Combination therapy for cancer comprising a platinum -based antineoplastic agent and a biocompatible electron donor |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20050070385A (en) | 2005-07-07 |
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