[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content
Springer Nature Link
Log in

Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression

  • Research Article
  • Published:
Tumor Biology

Abstract

Baicalein, a flavonoid compound, is one of the active constituents of the root of Scutellariae Radix. Its antitumor effects have attracted widespread attention worldwide. One of its major functions is to induce the apoptosis of tumor cells, but the antitumor mechanism is currently unclear. In the present study, we found that baicalein increased MG-63 cell mortality in a dose-dependent manner. Meanwhile, baicalein activated apoptosis through induced intracellular reactive oxygen species (ROS) generation, and that ROS scavenger N-acetyl-cysteine (NAC), glutathione (GSH), and superoxide dismutase (SOD) apparently inhibited intracellular ROS production, consequently attenuating the baicalein-induced apoptosis. Baicalein also induce the mitochondrial fragmentation which precedes the cell apoptosis. This morphological alteration is accompanied by an increase in the expression of the protein BNIP3 as well as Mul1 and Drp1. Furthermore, we show that the inhibition of BNIP3 expression can inhibit cell apoptosis by baicalein treatment. Taken together, our results bring the evidence of a mechanism that links apoptosis and ROS-induced BNIP3 expression in MG-63 cells with bacalein treatment and suggest that baicalein has a good potential as an anti-osteosarcoma drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ROS:

Reactive oxygen species

NAC:

N-acetyl-cysteine

GSH:

Glutathione

SOD:

Superoxide dismutase

BNIP3:

BCL2/adenovirus E1B 19 kDa interacting protein 3

LDH:

Lactate dehydrogenase

References

  1. Oertel S, Blattmann C, Rieken S, Jensen A, Combs SE, Huber PE, et al. Radiotherapy in the treatment of primary osteosarcoma—a single center experience. Tumori. 2010;96:582.

    PubMed  Google Scholar 

  2. Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007;70:461–77.

    Article  CAS  PubMed  Google Scholar 

  3. Kim YO, Leem K, Park J, Lee P, Ahn D-K, Lee BC, et al. Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. J Ethnopharmacol. 2001;77:183–8.

    Article  CAS  PubMed  Google Scholar 

  4. Chen Z-Y, Su Y-L, Lau C-W, Law W-I, Huang Y. Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Eur J Pharmacol. 1999;374:41–7.

    Article  CAS  PubMed  Google Scholar 

  5. Lin C-C, Shieh D-E. The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. The American journal of Chinese medicine. 1996;24:31–6.

    Article  CAS  PubMed  Google Scholar 

  6. Waisundara VY, Siu SY, Hsu A, Huang D, Tan BK. Baicalin upregulates the genetic expression of antioxidant enzymes in type-2 diabetic Goto-Kakizaki rats. Life Sci. 2011;88:1016–25.

    Article  CAS  PubMed  Google Scholar 

  7. Kim DH, Chung HY, Cho KH, Moon SK, Kim YS, Kim DH, et al. Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite. J Pharm Pharmacol. 2005;57:1581–90.

    Article  CAS  PubMed  Google Scholar 

  8. Chow J-M, Shen S-C, Wu C-Y, Chen Y-C. 12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells. Apoptosis. 2006;11:1999–2011.

    Article  CAS  PubMed  Google Scholar 

  9. Lee J-H, Li Y-C, Ip S-W, Hsu S-C, Chang N-W, Tang N-Y, et al. The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria-and caspase-3-dependent pathway. Anticancer Res. 2008;28:1701–11.

    CAS  PubMed  Google Scholar 

  10. J-Y CHUANG, Y-Y TSAI, S-C CHEN, T-J HSIEH, J-G CHUNG. Induction of G0/G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma (HeLa) cells. In Vivo. 2005;19:683–8.

    Google Scholar 

  11. Zhang H, Chen H, Luo H, An J, Sun L, Mei L, et al. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II. Hum Genet. 2012;131:491–503. doi:10.1007/s00439-011-1098-2.

    Article  CAS  PubMed  Google Scholar 

  12. Wang J, Yu Y, Hashimoto F, Sakata Y, Fujii M, Hou D-X. Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. International journal of molecular medicine. 2004;14:627.

    PubMed  Google Scholar 

  13. Esmaeili MA, Farimani MM, Kiaei M. Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochem. 2014;1–15.

  14. Ma W-D, Zou Y-P, Wang P, Yao X-H, Sun Y, Duan M-H, et al. Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway. Food Chem Toxicol. 2014;70:1–8.

    Article  CAS  PubMed  Google Scholar 

  15. Wu S, Zhou F, Zhang Z, Xing D. Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission–fusion proteins. FEBS J. 2011;278:941–54.

    Article  CAS  PubMed  Google Scholar 

  16. Ghavami S, Eshragi M, Ande SR, Chazin WJ, Klonisch T, Halayko AJ, et al. S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res. 2009;20:314–31.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Broadhead ML, Clark JC, Dass CR, Choong PF, Myers DE. Therapeutic targeting of osteoclast function and pathways. Expert Opin Ther Targets. 2011;15:169–81.

    Article  PubMed  Google Scholar 

  18. Takahashi H, Chen MC, Pham H, Angst E, King JC, Park J, et al. Baicalein, a component of Scutellaria baicalensis induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochimica et Biophysica Acta (BBA)-Molecular. Cell Res. 2011;1813:1465–74.

    CAS  Google Scholar 

  19. Kuo H-M, Tsai H-C, Lin Y-L, Yang J-S, Huang A-C, Yang M-D, et al. Mitochondrial-dependent caspase activation pathway is involved in baicalein-induced apoptosis in human hepatoma J5 cells. Int J Oncol. 2009;35:717–24.

    CAS  PubMed  Google Scholar 

  20. Zhang Y, Song L, Cai L, Wei R, Hu H, Jin W (2012) Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells. Food Chem Toxicol.

  21. Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009;35:57–68.

    Article  CAS  PubMed  Google Scholar 

  22. Bedard K, Krause K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.

    Article  CAS  PubMed  Google Scholar 

  23. Han Y, Chen JZ (2012) Oxidative stress induces mitochondrial DNA damage and cytotoxicity through independent mechanisms in human cancer cells. BioMed Res Int 2013

  24. Reed J. Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death & Differentiation. 2006;13:1378–86.

    Article  CAS  Google Scholar 

  25. Kubli D, Ycaza J. Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak. Biochem J. 2007;405:407–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jisun L, Samantha G, Jianhua Z. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J. 2012;441:523–40.

    Article  Google Scholar 

Download references

Conflicts of interest

None

Authors’ contributions

Fangfan Ye drafted the article. Honghan Wang, Lusi Zhang, Yongyi Zou, and HaiLong Han were in charge in acquisition of data, analysis and interpretation of data, and revision of the article. Jia Huang took control in the conception and design.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China

    Fangfan Ye

  2. Department of Head and Neck Surgery, Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China

    Honghan Wang

  3. Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Lusi Zhang

  4. State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China

    Yongyi Zou & Hailong Han

  5. Department of Critical Care Medicine, Second Xiangya Hospital, Central South University, Renmin Road 139, Changsha, 410011, Hunan, China

    Jia Huang

Authors
  1. Fangfan Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Honghan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lusi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yongyi Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hailong Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jia Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jia Huang.

Additional information

Guarantor of submission

The corresponding author is the guarantor of submission.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ye, F., Wang, H., Zhang, L. et al. Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression. Tumor Biol. 36, 4731–4740 (2015). https://doi.org/10.1007/s13277-015-3122-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3122-y

Keywords

Search

Navigation