Skip to main content
Log in

(−)-Epigallocatechin (EGC) of Green Tea Induces Apoptosis of Human Breast Cancer Cells But Not of their Normal Counterparts

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

(−)-Epigallocatechin (EGC), one of green tea polyphenols, has been shown to inhibit growth of cancer cells. However its mechanism of action is poorly known. We show here that EGC strongly inhibited the growth of breast cancer cell lines (MCF-7 and MDA-MB-231) but not that of normal breast epithelial cells. The inhibition of breast cancer cell growth was due to an induction of apoptosis, without any change in cell cycle progression. MCF-7 cells are known to express a wild-type p53 whereas MDA-MB-231 cells express a mutated p53. The fact that EGC induced apoptosis in both these cell lines suggests that the EGC-triggered apoptosis is independent of p53 status. Moreover, neutralizing antibodies against the death receptor Fas and inhibitors of caspases, such as caspase-8 and -10, efficiently inhibited the EGC-triggered apoptosis. In addition, immunoblotting revealed that EGC treatment was correlated with a decrease in Bcl-2 and an increase in Bax level. These results suggest that EGC-triggered apoptosis in breast cancer cells requires Fas signaling.

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.

Similar content being viewed by others

References

  1. Stoner GD, Mukhtar H: Polyphenols as cancer chemopreven-tive agents. J Cell Biochem 22(suppl): 169–180, 1995

    Google Scholar 

  2. Katiyar SK, Mukhtar H: Tea in chemoprevention of can-cer: epidemiologic and experimental studies. Int J Oncol 8: 221–238, 1996 (Review)

    Google Scholar 

  3. Bushman JL: Green tea and cancer in humans: a review of literature. Nutr Cancer 31: 151–159, 1998

    PubMed  Google Scholar 

  4. Gupta S, Ahmad N, Mukhtar H: Prostate cancer chemopreven-tion by green tea. Semin Urol Oncol 17: 70–76, 1999

    PubMed  Google Scholar 

  5. Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y: Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res 89: 254–261, 1998

    PubMed  Google Scholar 

  6. Zhao B, Guo Q, Xin W: Free radical scavenging by green tea polyphenols. Method Enzymol 338: 204–217, 2001

    Google Scholar 

  7. Serafini M, Ghiselli A, Ferro-Luzzi A: In vivo antioxidant ef-fect of green and black tea in man. Eur J Clin Nutr 50: 28–32, 1996

    PubMed  Google Scholar 

  8. Wang ZY, Cheng SJ, Zhou ZC, Athar M, Khan WA, Bickers DR, Mukhtar H: Antimutagenic activity of green tea polyphenols. Mutat Res 223: 273–285, 1989.

    PubMed  Google Scholar 

  9. Kuroda Y, Hara Y: Antimutagenic and anticarcinogenic activ-ity of tea polyphenols. Mutat Res 436: 69–97, 1999

    PubMed  Google Scholar 

  10. Rice-Evans CA, Miller NJ, Paganga G: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biol Med 20: 933–956, 1996

    Google Scholar 

  11. Chen ZP, Schell JB, Ho CT, Chen KY: Green tea epigallocat-echin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett 129: 173–179, 1998

    PubMed  Google Scholar 

  12. Khafif A, Schantz SP, Chou TC, Edelstein D, Sacks PG: Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalig-nant and malignant human oral epithelial cells. Carcinogenesis 19: 419–424, 1998

    PubMed  Google Scholar 

  13. Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H: Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst 89: 1881–1886, 1997

    PubMed  Google Scholar 

  14. Yang GY, Liao L, Kim K, Yurkow EJ, Yang CS: Inhibition of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 19: 611–616, 1998

    PubMed  Google Scholar 

  15. Ahmad N, Gupta S, Mukhtar H: Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Arch Bio-chem Biophys 376: 338–346, 2000

    Google Scholar 

  16. Valcic S, Timmermann BN, Alberts DS, Wächter GA, Krutzsch M, Wymer J, Guillèn JM: Inhibitory effect of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs 7: 461–468, 1996

    PubMed  Google Scholar 

  17. Dong-Le Bourhis X, Berthois Y, Millot G, Degeorges A, Sylvi M, Martin PM, Calvo F: Effect of stromal and epithelial cells derived from normal and tumorous breast tissue on the prolif-eration of human breast cancer cell lines in co-culture. Int J Cancer 71: 42–48, 1997

    PubMed  Google Scholar 

  18. Descamps S, Toillon RA, Adriaenssens E, Pawlowski V, Cool SM, Nurcombe V, Le Bourhis X, Boilly B, Peyrat JP, Hondermarck H: Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways. J Biol Chem 276: 17,864–17,870, 2001

    Google Scholar 

  19. Toillon RA, Adriaenssens E, Wouters D, Lottin S, Boilly B, Hondermarck H, Le Bourhis X: Normal breast epithelial cells induce apoptosis of MCF-7 breast cancer cells through a p53-mediated pathway. Mol Cell Biol Res Commun 3: 338–344, 2000

    PubMed  Google Scholar 

  20. Wesselborg S, Engels IH, Rossmann E, Los M, Schulze-Osthoff K: Anticancer drugs induce caspase-8/FLICE activa-tion and apoptosis in the absence of CD95 receptor/ligand interaction. Blood 93: 3053–3063, 1999

    PubMed  Google Scholar 

  21. Shao RG, Cao CX, Nieves-Neira W, Dimanche-Boitrel MT, Solary E, Pommier Y: Activation of the Fas pathway indepen-dently of Fas ligand during apoptosis induced by camptothecin in p53 mutant human colon carcinoma cells. Oncogene 20: 1852–1859, 2001

    PubMed  Google Scholar 

  22. Juo P, Kuo CJ, Yuan J, Blenis J: Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr Biol 8: 1001–1008, 1998

    PubMed  Google Scholar 

  23. Okabe S, Suganuma M, Hayashi M, Sueoka E, Komori A, Fujiki H: Mechanisms of growth inhibition of human lung cancer cell line, PC-9, by tea polyphenols. Jpn J Cancer Res 88: 639–643, 1997

    PubMed  Google Scholar 

  24. Fujiki H, Suganuma M, Okabe S, Sueoka N, Komori A, Sueoka E, Kozu T, Tada Y, Suga K, Imai K, Nakachi K: Cancer inhibition by green tea. Mutat Res 402: 307–310, 1998

    PubMed  Google Scholar 

  25. Johnston SR: Acquired tamoxifen resistance in human breast cancer - potential mechanisms and clinical implications. Anticancer Drugs 8: 911–930, 1997

    PubMed  Google Scholar 

  26. England GM, Jordan VC: Pure antiestrogens as a new therapy for breast cancer. Oncol Res 9: 397–402, 1997

    PubMed  Google Scholar 

  27. Weller M: Predicting response to cancer chemotherapy: the role of p53. Cell Tissue Res 292: 435–445, 1998

    PubMed  Google Scholar 

  28. Pirollo KF, Bouker KB, Chang EH: Does p53 status influence tumor response to anticancer therapies? Anticancer Drugs 11: 419–432, 2000

    PubMed  Google Scholar 

  29. Ozbun MA, Butel JS: Tumor suppressor p53 mutations and breast cancer: a critical analysis. Adv Cancer Res 66: 71–141, 1995

    PubMed  Google Scholar 

  30. Hartmann A, Blaszyk H, Kovach JS, Sommer SS: The mo-lecular epidemiology of p53 gene mutations in human breast cancer. Trends Genet 13: 27–33, 1997

    PubMed  Google Scholar 

  31. Adams JM, Cory S: The Bcl-2 protein family: arbiters of cell survival. Science 281: 1322–1326, 1998

    PubMed  Google Scholar 

  32. Kroemer G, Reed JC: Mitochondrial control of cell death. Nat Med 6: 513–519, 2000

    PubMed  Google Scholar 

  33. Nagata S, Golstein P: The Fas death factor. Science 267: 1449–1456, 1995

    PubMed  Google Scholar 

  34. Hayakawa S, Saeki K, Sazuka M, Suzuki Y, Shaoji Y, Ohta T, Kaji K, Yuo A, Isemura M: Apoptosis induction by epigallocatechin gallate involves its binding to Fas. Biochem Biophys Res Comm 285: 1102–1106, 2001

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vergote, D., Cren-Olivé, C., Chopin, V. et al. (−)-Epigallocatechin (EGC) of Green Tea Induces Apoptosis of Human Breast Cancer Cells But Not of their Normal Counterparts. Breast Cancer Res Treat 76, 195–201 (2002). https://doi.org/10.1023/A:1020833410523

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020833410523

Navigation