Skip to main content

Advertisement

Log in

Epigallocatechin-3-gallate Sensitizes Human 786-O Renal Cell Carcinoma Cells to TRAIL-Induced Apoptosis

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, potentiating effect of EGCG on TRAIL-induced apoptosis human renal carcinoma cell line 786-O which is relatively resistant to TRAIL was examined, and the possible mechanism was investigated. Here, we show that co-treatment with EGCG and TRAIL induced significantly more profound apoptosis in 786-O cells. Treatment of 786-O cells with EGCG and TRAIL downregulated c-FLIP, Mcl-1, and Bcl-2 proteins in a caspase-dependent pathway. Moreover, we found that pretreatment with NAC markedly inhibited the expression levels of c-FLIP, Mcl-1, and Bcl-2 downregulated by the combinatory treatment, suggesting that the regulating effect of EGCG on these above apoptosis-relevant molecules was partially mediated by generation of ROS. Taken together, the present study demonstrates that EGCG sensitizes human 786-O renal cell carcinoma cells to TRAIL-induced apoptosis by downregulation of c-FLIP, Mcl-1, and Bcl-2.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Xue, Y. J., Xiao, R. H., Long, D. Z., Zou, X. F., Wang, X. N., Zhang, G. X., et al. (2012). Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma. Journal of Translational Medicine, 10, 200.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Girgis, A. H., Iakovlev, V. V., Beheshti, B., Bayani, J., Squire, J. A., Bui, A., et al. (2012). Multilevel whole-genome analysis reveals candidate biomarkers in clear cell renal cell carcinoma. Cancer Research, 72, 5273–5284.

    Article  CAS  PubMed  Google Scholar 

  3. Requena, M. J., Carrasco, J. C., & Alvarez-Kindelan, J. (2008). Role of molecular markers in diagnosis and prognosis of renal cell carcinoma. Analytical and Quantitative Cytology and Histology/The International Academy of Cytology [and] American Society of Cytology, 30, 336–337.

    Google Scholar 

  4. Lang, K., Danchenko, N., Gondek, K., Schwartz, B., & Thompson, D. (2007). The burden of illness associated with renal cell carcinoma in the United States. Urologic Oncology, 25, 368–375.

    Article  PubMed  Google Scholar 

  5. Amen, K. (2007). Managing the complex journey of renal cell carcinoma. ONS Connect, 22, 53–54.

    PubMed  Google Scholar 

  6. Takahashi, M., Rhodes, D. R., Furge, K. A., Kanayama, H., Kagawa, S., Haab, B. B., & Teh, B. T. (2001). Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification. Proceedings of the National Academy of Sciences of the United States of America, 98, 9754–9759.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Tan, M. L., Ooi, J. P., Ismail, N., Moad, A. I., & Muhammad, T. S. (2009). Programmed cell death pathways and current antitumor targets. Pharmaceutical Research, 26, 1547–1560.

    Article  CAS  PubMed  Google Scholar 

  8. Wu, G. S. (2009). TRAIL as a target in anti-cancer therapy. Cancer Letters, 285, 1–5.

    Article  CAS  PubMed  Google Scholar 

  9. Deng, Y., Lin, Y., & Wu, X. (2002). TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. Genes & Development, 16, 33–45.

    Article  CAS  Google Scholar 

  10. Khan, N., & Mukhtar, H. (2013). Modulation of signaling pathways in prostate cancer by green tea polyphenols. Biochemical Pharmacology, 85, 667–672.

    Article  CAS  PubMed  Google Scholar 

  11. Katiyar, S. K., Perez, A., & Mukhtar, H. (2000). Green tea polyphenol treatment to human skin prevents formation of ultraviolet light B-induced pyrimidine dimers in DNA. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 6, 3864–3869.

    CAS  Google Scholar 

  12. Ahmad, N., Gupta, S., & Mukhtar, H. (2000). Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Archives of Biochemistry and Biophysics, 376, 338–346.

    Article  CAS  PubMed  Google Scholar 

  13. Ahmad, N., Feyes, D. K., Nieminen, A. L., Agarwal, R., & Mukhtar, H. (1997). Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. Journal of the National Cancer Institute, 89, 1881–1886.

    Article  CAS  PubMed  Google Scholar 

  14. Siddiqui, I. A., Adhami, V. M., Afaq, F., Ahmad, N., & Mukhtar, H. (2004). Modulation of phosphatidylinositol-3-kinase/protein kinase B- and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells. Journal of Cellular Biochemistry, 91, 232–242.

    Article  CAS  PubMed  Google Scholar 

  15. Hastak, K., Gupta, S., Ahmad, N., Agarwal, M. K., Agarwal, M. L., & Mukhtar, H. (2003). Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene, 22, 4851–4859.

    Article  CAS  PubMed  Google Scholar 

  16. Shimizu, M., Deguchi, A., Lim, J. T., Moriwaki, H., Kopelovich, L., & Weinstein, I. B. (2005). (-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 11, 2735–2746.

    Article  CAS  Google Scholar 

  17. Jung, Y. D., Kim, M. S., Shin, B. A., Chay, K. O., Ahn, B. W., Liu, W., et al. (2001). EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. British Journal of Cancer, 84, 844–850.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Sartippour, M. R., Shao, Z. M., Heber, D., Beatty, P., Zhang, L., Liu, C., et al. (2002). Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells. The Journal of Nutrition, 132, 2307–2311.

    CAS  PubMed  Google Scholar 

  19. Lee, Y. K., Bone, N. D., Strege, A. K., Shanafelt, T. D., Jelinek, D. F., & Kay, N. E. (2004). VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG) B-cell chronic lymphocytic leukemia. Blood, 104, 788–794.

    Article  CAS  PubMed  Google Scholar 

  20. Vayalil, P. K., & Katiyar, S. K. (2004). Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-kappaB in human prostate carcinoma DU-145 cells. The Prostate, 59, 33–42.

    Article  CAS  PubMed  Google Scholar 

  21. Clark, P. E., Polosukhina, D. A., Gyabaah, K., Moses, H. L., Thorburn, A., & Zent, R. (2010). TRAIL and interferon-alpha act synergistically to induce renal cell carcinoma apoptosis. The Journal of Urology, 184, 1166–1174.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Zhang, Y., Yang, N. D., Zhou, F., Shen, T., Duan, T., Zhou, J., et al. (2012). (-)-Epigallocatechin-3-gallate induces non-apoptotic cell death in human cancer cells via ROS-mediated lysosomal membrane permeabilization. PLoS One, 7, e46749.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Manohar, M., Fatima, I., Saxena, R., Chandra, V., Sankhwar, P. L., & Dwivedi, A. (2013). (-)-Epigallocatechin-3-gallate induces apoptosis in human endometrial adenocarcinoma cells via ROS generation and p38 MAP kinase activation. The Journal of Nutritional Biochemistry, 24, 940–947.

    Article  CAS  PubMed  Google Scholar 

  24. Li, W., Nie, S., Yu, Q., & Xie, M. (2009). (-)-Epigallocatechin-3-gallate induces apoptosis of human hepatoma cells by mitochondrial pathways related to reactive oxygen species. Journal of Agricultural and Food Chemistry, 57, 6685–6691.

    Article  CAS  PubMed  Google Scholar 

  25. Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C. P., Nicholl, J. K., et al. (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity, 3, 673–682.

    Article  CAS  PubMed  Google Scholar 

  26. Pan, G., O’Rourke, K., Chinnaiyan, A. M., Gentz, R., Ebner, R., Ni, J., & Dixit, V. M. (1997). The receptor for the cytotoxic ligand TRAIL. Science, 276, 111–113.

    Article  CAS  PubMed  Google Scholar 

  27. Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A., Skubatch, M., Baldwin, D., et al. (1997). Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science, 277, 818–821.

    Article  CAS  PubMed  Google Scholar 

  28. Pan, G., Ni, J., Wei, Y. F., Yu, G., Gentz, R., & Dixit, V. M. (1997). An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science, 277, 815–818.

    Article  CAS  PubMed  Google Scholar 

  29. Toiyama, D., Takaha, N., Shinnoh, M., Ueda, T., Kimura, Y., Nakamura, T., et al. (2013). Significance of serum tumor necrosis factor-related apoptosis-inducing ligand as a prognostic biomarker for renal cell carcinoma. Molecular and Clinical Oncology, 1, 69–74.

    PubMed Central  PubMed  Google Scholar 

  30. Macher-Goeppinger, S., Aulmann, S., Tagscherer, K. E., Wagener, N., Haferkamp, A., Penzel, R., et al. (2009). Prognostic value of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors in renal cell cancer. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 15, 650–659.

    Article  CAS  Google Scholar 

  31. Birt, D. F., Hendrich, S., & Wang, W. (2001). Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacology & Therapeutics, 90, 157–177.

    Article  CAS  Google Scholar 

  32. Li, Y., Fang, H., & Xu, W. (2007). Recent advance in the research of flavonoids as anticancer agents. Mini Reviews in Medicinal Chemistry, 7, 663–678.

    Article  CAS  PubMed  Google Scholar 

  33. Kelemen, K., Kiesecker, C., Zitron, E., Bauer, A., Scholz, E., Bloehs, R., et al. (2007). Green tea flavonoid epigallocatechin-3-gallate (EGCG) inhibits cardiac hERG potassium channels. Biochemical and Biophysical Research Communications, 364, 429–435.

    Article  CAS  PubMed  Google Scholar 

  34. Yuan, J. M. (2011). Green tea and prevention of esophageal and lung cancers. Molecular Nutrition & Food Research, 55, 886–904.

    Article  CAS  Google Scholar 

  35. Gu, B., Ding, Q., Xia, G., & Fang, Z. (2009). EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. Oncology Reports, 21, 635–640.

    CAS  PubMed  Google Scholar 

  36. Kim, Y. S., Kim, E. A., Park, K. G., Lee, S. J., Kim, M. S., Sohn, H. Y., & Lee, T. J. (2012). Dioscin sensitizes cells to TRAIL-induced apoptosis through downregulation of c-FLIP and Bcl-2. Oncology Reports, 28, 1910–1916.

    CAS  PubMed  Google Scholar 

  37. Son, Y. G., Kim, E. H., Kim, J. Y., Kim, S. U., Kwon, T. K., Yoon, A. R., et al. (2007). Silibinin sensitizes human glioma cells to TRAIL-mediated apoptosis via DR5 up-regulation and down-regulation of c-FLIP and survivin. Cancer Research, 67, 8274–8284.

    Article  CAS  PubMed  Google Scholar 

  38. Ou, Y. C., Li, J. R., Kuan, Y. H., Raung, S. L., Wang, C. C., Hung, Y. Y., et al. (2014). Luteolin sensitizes human 786-O renal cell carcinoma cells to TRAIL-induced apoptosis. Life Sciences, 100, 110–117.

    Article  CAS  PubMed  Google Scholar 

  39. Poukkula, M., Kaunisto, A., Hietakangas, V., Denessiouk, K., Katajamaki, T., Johnson, M. S., et al. (2005). Rapid turnover of c-FLIP short is determined by its unique C-terminal tail. The Journal of Biological Chemistry, 280, 27345–27355.

    Article  CAS  PubMed  Google Scholar 

  40. Li, W., Zhang, X., & Olumi, A. F. (2007). MG-132 sensitizes TRAIL-resistant prostate cancer cells by activating c-Fos/c-Jun heterodimers and repressing c-FLIP(L). Cancer Research, 67, 2247–2255.

    Article  CAS  PubMed  Google Scholar 

  41. Benayoun, B., Baghdiguian, S., Lajmanovich, A., Bartoli, M., Daniele, N., Gicquel, E., et al. (2008). NF-kappaB-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 22, 1521–1529.

    Article  CAS  Google Scholar 

  42. Nitobe, J., Yamaguchi, S., Okuyama, M., Nozaki, N., Sata, M., Miyamoto, T., et al. (2003). Reactive oxygen species regulate FLICE inhibitory protein (C-FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes. Cardiovascular Research, 57, 119–128.

    Article  CAS  PubMed  Google Scholar 

  43. Kanayama, A., & Miyamoto, Y. (2007). Apoptosis triggered by phagocytosis-related oxidative stress through C-FLIPS down-regulation and JNK activation. Journal of Leukocyte Biology, 82, 1344–1352.

    Article  CAS  PubMed  Google Scholar 

  44. Satoh, M., Takemura, Y., Hamada, H., Sekido, Y., & Kubota, S. (2013). EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy. Cancer Cell International, 13, 19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruojing Wei.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, R., Zhu, G., Jia, N. et al. Epigallocatechin-3-gallate Sensitizes Human 786-O Renal Cell Carcinoma Cells to TRAIL-Induced Apoptosis. Cell Biochem Biophys 72, 157–164 (2015). https://doi.org/10.1007/s12013-014-0428-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0428-0

Keywords

Navigation