JPH03287526A - Preventive of carcinogenesis - Google Patents

Abstract

PURPOSE:To obtain a new preventive of carcinogenesis having anticarcinogenic promotion action, comprising naturally occurring panaxynol as an active ingredient. CONSTITUTION:A preventive of carcinogenesis comprising naturally occurring panaxynol shown by the formula, falcarinol as an another name, as an active ingredient. Panaxynol is contained in a plant such as Panax ginseng, Daucus caroto, Saposhnikovia divaricata, Schefflera arboricola or Bedera helix and is obtained by extracting the plant. Panaxynol can strongly control EpsteinBarr virus by etradecanoylphorbol acetate and is usable for the purpose of prevention of carcinogenesis. The preventive of carcinogenesis is used as a drug of preventing carcinogenesis and a food preventing carcinogenesis.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a carcinogenesis preventive agent, and more particularly to a novel carcinogenesis preventive agent having an anticarcinogenic effect.

(Prior art and the problem to be solved by the invention) Regarding adult diseases and cancer, it has been pointed out that early detection and early treatment are necessary. It is thought that normal cells have already been damaged by cancer-causing factors, and as a result, they harbor potential tumor cells that have almost irreversibly changed from normal cells. It is also generally accepted that these potential tumor cells undergo further epigenetic effects and transform into tumor cells, and this process is called promotion.

On the other hand, Epstein-Barr virus (EBV), which belongs to the herpesvirus family, is known as a virus that is said to cause Burkitt's lymphoma and nasopharyngeal cancer. This virus is a ubiquitous human virus that is latently distributed not only among these cancer patients but also throughout the world, and it is said that almost all adults are infected with EBV.

It has become clear that EBV targets normal human B lymphocytes, converts them into blast cells, and gives them unlimited proliferation potential. It is defined as a common viral factor. EBV-infected B lymphocytes undergo the above-mentioned promotion and migrate to cancer cells, and the presence of phorbol esters such as tetradecanoylphorbol acetate (TPA) as promoters has been shown epidemiologically and experimentally. has also been proven.

For example, East Africa.

Plants of the Euphorbiaceae family distributed in Rica contain phorbol esters, and the surrounding soil, crops, and drinking water are contaminated with the phorbol esters secreted by these plants. Kit lymphoma is occurring frequently. Therefore, it is extremely important how to prevent such promosilan in daily life, and the importance of primary prevention centered on improving dietary habits has recently been particularly emphasized. The present inventors have focused on the promosilane process of chemical carcinogenesis from the viewpoint of carcinogenesis prevention, and have been searching for carcinogenic promosilane inhibitors from natural resources. It has been found that aldehydes such as polygodial from Salix japonica and monoglycerides such as monolyruine from pigeon wheat can serve as anti-carcinogenic promoters. However, the search for naturally occurring anti-carcinogenic promoters has only just begun, and it cannot be said that sufficient studies have been conducted even on plants that are commonly used in daily life. - It has been desired to provide a carcinogenic preventive agent that has anti-carcinogenic effects.

(Means for Solving the Problems) The present inventors have developed B lymphocyte culture cells derived from Burkitt's lymphoma that contain the EBV genome.
) strain and used an experimental system with TPA as the oncogenic promoter to search for naturally occurring anti-carcinogenic promoters. More specifically, the Raji strain culture system is cultured with the addition of n-butyric acid, which has a synergistic effect on the expression of TPA and promosilane activity, and the test substance, and the early stages of EB virus, which is activated by TPA and expressed on the cell surface, are cultured. antigen (EBV-EA),
This is an observation method using indirect fluorescent antibody method using antibodies derived from nasopharyngeal cancer patient serum. EBV discovered by nature
Most of the activation inhibitors inhibit tumor development even in a two-step carcinogenesis experiment using TPA, and are effective as anti-carcinogenic promoters (Omoide, et al., Author: Antimutagienesis and Anticarcinogenesis).・Mechanisms ■, Blenheim Press, 425-429,
Page, 1990).

As a result of intensive research, the present inventors discovered a cancer prevention agent containing panaxinol as an active ingredient, and were able to solve the problem. Panaxinol is a well-known acetylene compound having the structure shown in the following formula.
Also called lcarinol).

CH,=CH HO-C(CmiC)tcu.

HC1( (Z)11 CH (CH*) @ CH.

Plants containing the above-mentioned compounds include Panax ginseng, Falcaria
Falcaria vulgaris
, Carrot (Daucus carota), Saposhnikovia divarie (Saposhnikovia divarie)
ata), Schefflera a.
rboricola) Gerard's Sow (Aegopod)
ium podagraria), ivy (Ile
dera helix) and the like, and extraction production from these plants can be achieved by a known solvent extraction method or a combination of two types of chromatography. For example, it can be obtained by extracting the whole plant of Hamaboufuu with methanol, partitioning the resulting extract between n-hexane and water, and separating and purifying the hexane fraction by normal phase and reverse phase column chromatography. . The main physical properties of panaxinol thus obtained are shown below.

FD-MS (m/z): 244, 227.112.60°IR (t'Jac1.cm-"): 3388, 2932.2256.1464.1286.
1118.984°H-NMR (CDCIs) ・
δ 0.88 (3B, t-1ike, J=6Hz),
1.27 (IOH, m).

2.02 (211, dt-1ike, J=6.811
z, 6.811z), 3.03(21d, J=6
．． 8Hz), 4.9 (1B, br, s), 5.2
4(d, J=10.7Hz), 5.33-5.56
(311, m), 5.94 (Ill, ddd-1ik
e, J=4.9Hz, 8.5Hz, 17.5Hz
).

lcoC-NMR (CDCIs) δ.

14.1.1? , 7.22.7.27.2.29.1.
29.2.29.3゜31.8.63.6.64.0.
71.3.74.3.80.3.117.0°], 22
．． 0.133.1.136.2.

Furthermore, plant extracts containing panaxinol as an active ingredient can also be used as anti-carcinogenic promoters. These plant extracts are made by extracting the plant body containing vanaxinol with water, methanol, ethanol, acetate,
It can be obtained by extraction using an organic solvent such as acetone, methyl ethyl ketone, or a mixed solvent thereof. Furthermore, if necessary, a fraction in which the active ingredient is concentrated can be obtained by known separation means.

The anti-carcinogenic promoter thus obtained can be used as a carcinogenic preventive agent in the form of a composition containing an effective and non-toxic amount thereof.For example, oral preparations include tablets, capsules, troches, It can be used as solid preparations such as granules and powders, or liquid preparations such as solutions and syrups. The proportion of anti-carcinogenic promoters in the carcinogenic preventive agent of the present invention varies depending on the type, but usually when taken orally.

In this case, a suitable amount is 0.3 to 15% by weight. The amount of intake varies depending on the desired preventive effect and age, but for adults it is usually 1
0.5 to 50 per day as the above anti-carcinogenic promoter
Use in the range of 00mg.

Next, the method for producing vanaxinol of the present invention and its EBV activation inhibitory effect will be explained using test methods and examples.

(Test method) RPM11640 with fetal serum and antibiotics added was used as a culture medium for EBV latently infected human lymphoblastoid cell line Raji cells. Under these culture conditions, EBV-
EA eye silent expression rate is 0.1% or less. IX1
Raji cells adjusted to a concentration of 0@cells/ml were added to 4 m
The cells were cultured at 37° C. for 48 hours in the above-mentioned culture medium containing M n-butyric acid, 20 ng/rnl TPA, and the test substance added thereto at a concentration of 1 to 100 μg/ml. EBV-EA was stained by indirect fluorescent antibody method using nasopharyngeal cancer patient serum, and the percentage of positive cells was calculated relative to a control to which no test substance was added, and was taken as EBV activation inhibitory activity.

(Example 1) A whole plant (290 g) of Japanese-produced Hamaboufu was immersed in methanol, and two weeks later, it was filtered, and the solvent was distilled off from the filtrate by concentration to obtain an extract (10 g).

Using this, EBV activation inhibitory activity was measured according to the above test method (Table 1).

(Example 2) The extract (10 g) obtained in Example 1 was mixed with methanol and n
-Hexane, and the solvent was distilled off from the hexane fraction to obtain an extract (0.73 g).

Using this, EBV activation inhibitory activity was measured according to the above test method (Table 1).

(Example 3) The extract (49 g) obtained in Example 2 was subjected to silica gel column chromatography using a solvent system of cyclohexane/ethyl acetate (10:l+10.v/v). The fractions were further separated and purified by reverse-phase liquid chromatography, and water/methanol (1
0:3. A single compound was obtained from the fraction eluted with the eluent (v/v). This compound is IR, FD
It was identified as vanaxinol based on various spectral data such as -MS, "H-" and "-NMR."

Using this, EBV activation inhibitory activity was measured according to the above test method (Table 1).

Table 1 EBV activation inhibitory activity of test substance (%) Test substance (8 g) 00 0 Extract 5 of Example 1 Extract 1 of Example 2 6 Compound of Example 3 00 00 00 (Effect of the invention) Shown in Table 1 As described above, the panaxinol of the present invention is TPA
Since it strongly suppresses EBV activation by , it can be expected to be used as an anti-carcinogenic promoter for the purpose of preventing cancer development, and can also be used in cancer prevention drugs and cancer prevention foods.

Claims (1)

[Claims] A cancer prevention agent containing panaxynol (also known as falcarinol) as an active ingredient.