Short on time?

Get essay writing help

Discursive Essay on Antiproliferative Action of EGCG on Pancreatic Cancer Cells

Words: 2549
Pages: 6
This essay sample was donated by a student to help the academic community. Papers provided by EduBirdie writers usually outdo students' samples.


Cancer is described as a disease that is characterized by excessive proliferation of cells and of their inability to die. Normally, cells can kill themselves in a balanced process known as ‘apoptosis’. It is becoming clear that too little cell suicide by apoptotic process can lead to a variety of cancers, including pancreatic cancer. Further investigation suggested that EGCG has Antiproliferative action on pancreatic cancer cells and this Antiproliferative action is mediated through Programmed cell death or apoptosis. Although some studies indicate that the antiproliferative action of EGCG in pancreatic cancer was never investigated. More importantly, the present study unravels the involvement of mitochondria in the EGCG-induced apoptosis of pancreatic cancer cells. The novelty of our studies is the differential response of different pancreatic cancer cell lines to tea polyphenol. Thus, it would be of value to develop biomarkers of resistance in the course of mechanistic studies and to develop a sense of resistant phenotype. Studies are in progress in the laboratory to understand the mechanism of different sensitivities of pancreatic cancer cell lines to EGCG. The results of our studies involving pancreatic cancer are quite concordant with the previous observation implying that a direct inhibition of antiapoptotic Bcl-2 family proteins (1,2) except the necessity of higher concentration of EGCG in pancreatic cancer cells. The inhibition of Bcl-2 by EGCG might result in an up-regulation of pro-apoptotic member Bax. In addition, we noted an oligomerization of Bax along with cytochrome c release/change in the mitochondrial membrane potential in EGCG-treated cancer cells. The requirement of high concentration of EGCG to suppress cell proliferation or to induce apoptosis in pancreatic cancer cells might be due to the difference in the cell permeability of EGCG or sequestering of EGCG by other proteins yet to be identified. A previous study by Takada demonstrated the suppression of growth inhibition as well as invasion of pancreatic cancer cells, at 0.1--0.2 µM concentration of EGCG. Treatment with 0.2 µM EGCG resulted in suppression of the growth of PANC-1 (15.4%) and MIA PaCa-2 (26.0%) cells. It is to be noted that a 0.1 mM concentration of EGCG is often required to trigger stress signals in cancer cells. The prevention of EGCG-mediated apoptosis by JNK inhibitor II suggests the involvement of ROS-mediated JNK activation in this pathway. The ROS comprises of singlet oxygen, hydroxyl radicals, superoxide, hydroperoxides, and Peroxides. We have noted an increase in the hydrogen peroxide level owing to EGCG exposure as noted in the case of lung cancer cell lines have indicated that JNK signalling is necessary for the stress-induced release of cytochrome c release and programmed cell death. JNK signalling and cytochrome c release may be interlinked to a pro-apoptotic member of Bcl-2 family because activated JNK is unable to evoke apoptosis in cells deficient of Bax. Our observation indicates that the concerted efforts of JNK activation and Bax oligomerization might play a pivotal role in the demise of pancreatic cancer cells. At present, two major pathways that link apoptosis have been identified: (a) intrinsic or mitochondrial and (b) extrinsic or death receptor-related. The intrinsic pathway involves the cell sensing stress that triggers the mitochondria-dependent processes, resulting in cytochrome c release and activation of caspase-9. EGCG-induced apoptosis in some cancer cells might be orchestrated by the cooperative effects of both ‘extrinsic’ and ‘intrinsic’ pathways. To summarize, our data suggest that EGCG initiates the cell death process through cell cycle arrest at an earlier phase, as well as the oligomerization of pro-apoptotic regulator Bax, in pancreatic cancer. Perhaps, oligomeric Bax along with other pro-apoptotic members (Bak or Bid) form pores in the mitochondrial membrane to facilitate the release of apoptogenic factors from the mitochondria to cytosol. The permeabilization of the outer membrane is thought to be a major event in releasing proteins such as cytochrome c from the intermembrane space. Indeed, EGCG-induced apoptosis in pancreatic cancer cells is accompanied by the mitochondrial membrane depolarization and the release of cytochrome c from mitochondria into the cytosol. Cytochrome c is bound to the outer surface of the inner membrane phospholipids, primarily to cardiolipin molecules. Mechanistically, it is possible that ROS generation in mitochondria targets membrane lipid cardiolipin to dissociate cytochrome c. In pancreatic cancer cells as observed here, EGCG-mediated ROS production might play such a role. In a variety of cell types, the apoptosis triggering effects of ROS were noted in vitro. The very poor prognosis and high mortality that pancreatic cancer patients face results, in part, from our current inability to both identify individuals at increased risk for this disease and detect neoplasms earlier. The elucidation of the mechanism by which the existing chemopreventive agents decrease pancreatic tumor growth should facilitate the establishment of efficacious regimens for the inhibition of human pancreatic carcinoma. Apoptosis in EGCG-exposed pancreatic cancer cells might hold future promise for deploying green tea as a chemopreventive agent. The development of a chemopreventive agent in regular diet is very promising for pancreatic cancer since this spiteful form of human malignancy is often diagnosed very late. Thus, the induction of the cell death program by the polyphenol constituent of green tea might be helpful in evading the potential malignant outcome of genomic damage in pancreatic cancer.

Save your time!
We can take care of your essay
  • Proper editing and formatting
  • Free revision, title page, and bibliography
  • Flexible prices and money-back guarantee
Place Order


Chemoprevention, also defined as ‘‘slowing the process of carcinogenesis’’ is a concept that appears to be a viable option in control. To be effective in preventing cancer. Chemopreventive intervention should be addressed during the early stages of the carcinogenesis process. A plethora of experimental evidences suggest that a change in dietary and lifestyle factors prevents the Chronic inflammation and/or oxidative stress. Within the chemopreventive armamentarium, the use of natural agents from dietary sources is generally preferred with respect to bioactive molecules deriving from other sources. Many of these natural occurring agents demonstrate antioxidant activity, and compounds belonging to polyphenols chemical class may play a promising role in cancer prevention. Epidemiological studies conducted in humans supported the existence of an association between natural polyphenols consumption and a decrease in cancer rate. In the last decade, a representative member of polyphenols, i.e. EGCG, has been the focus of a number of studies scrutinizing its beneficial effects on health. Therefore, consumption of green tea has become more and more popular in the world due to its versatile health benefits. However, despite its neoplastic properties, EGCG presents important pharmacokinetic problems, due to inefficient systemic delivery and bioavailability. In order to improve the poor systemic bioavailability and cellular uptake of EGCG, various strategies have been adopted, which include combination therapy or polytherapy that consumes EGCG with one or more medications. In addition, recent studies conducted implying both EGCG and CSCs to found that EGCG induces multiple of anticancer effects in CSCs and enhances the chemo-sensitivity of chemo-drugs in CSCs. In this review the current available studies of the anti-cancer effects of EGCG alone and combined with other dietary and pharmaceutical agents as well other approaches used to deliver sustained levels of EGCG have been covered and discussed in order to introduce some furnish driving force for further evolution of research on innovative database able to consolidate the chemopreventive potential of EGCG.


  1. Leone,M., Zhai,D., Sareth,S., Kitada,S., Reed,J.C. and Pellecchia,M. (2003) Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res., 63, 8118--8121.
  2. Pellecchia, M. and Reed, J.C. (2004) Inhibition of anti-apoptotic Bcl-2 family proteins by natural polyphenols: new avenues for cancer chemoprevention and chemotherapy. Curr. Pharm. Des., 10, 1387--1398.
  3. Yang, C.S., Chung,J.Y., Yang, G., Chhabra, S.K. and Lee,M. J. (2000) Tea and tea polyphenols in cancer prevention. J. Nutr., 130, 472S--478S.
  4. Surh, Y.-J. (1999) Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat. Res., 428, 305--327.
  5. Fujiki,H., Suganuma,M., Okabe,S., Sueoka,N., Komori,A., Sueoka,E., Kozu,T., Tada,Y., Suga,K., Imai,K., and Nakachi,K. (1998) Cancer inhibition by green tea. Mutat. Res., 402, 307--310.
  6. Jankun,J., Selman,S.H., Swiercz,R. and Skrzypczak-Jankun,E. (1997) Why does drinking green tea prevent cancer? Nature, 387, 561.
  7. Wang, Z. Y., Huang, M.T., Ho, C.T., Chang, R., Ma, W., Ferraro, T., Reuhl, K.R., Yang, C.S. and Conney, A.H. (1992) Inhibitory effect of green tea on the growth of established skin papillomas in mice. Cancer Res., 52, 6657--6665.
  8. Nakachi, K., Suemasu, K., Suga, K., Takeo, T., Imai, K., and Higashi, Y. (1998) Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn. J. Cancer Res., 89, 254--261.
  9. Yang, C.S. (1997) Inhibition of carcinogenesis by tea. Nature, 389, 134--135.
  10. Fujiki,H., Yoshizawa,S., Horiuchi,T., Suganuma,M., Yatsunami,J., Nishiwaki,S., Okabe,S., Nishiwaki-Matsushima,R., Okuda,T. and Sugimura, T. (1992) Anticarcinogenic effects of (_)-epigallocatechin gallate. Prev. Med., 21, 503--509.
  11. Yamane,T., Nakatani,H., Kikuoka,N., Matsumoto,H., Iwata,Y., Kitao,Y., Oya,K. and Takahashi, T. (1996) Inhibitory effects and toxicity of green tea polyphenols for gastrointestinal carcinogenesis. Cancer, 77, 1662--1667.
  12. Jung, Y.D., Kim, M.S., Shin, B.A., Chay, K.O., Ahn, B.W., Liu, W., Bucana, C.D., Gallick, G.E. and Ellis, L.M. (2001) EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br. J. Cancer, 84, 844--850.
  13. Wang, Z.Y., Huang, M.T., Lou, Y.R., Xie, J.G., Reuhl, K.R., Newmark, H.L., Ho, C.T., Yang, C.S. and Conney, A.H. (1994) Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz (a)anthracene-initiated SKH-1 mice. Cancer Res., 54, 3428--3435.
  14. Katiyar, S.K., Mohan, R.R., Agarwal, R. and Mukhtar, H. (1997) Protection against induction of mouse skin papillomas with a low and high risk of conversion to malignancy by green tea polyphenols. Carcinogenesis, 18, 497--502.
  15. Sartippour, M.R., Heber, D., Ma, J., Lu, Q., Go, V.L., and Nguyen, M. (2001) Green tea and its catechins inhibit breast cancer xenografts. Nutr. Cancer, 40, 149--156.
  16. Hirose,M., Mizoguchi,Y., Yaono,M., Tanaka,H., Yamaguchi,T. and Shirai,T. (1997) Effects of green tea on the progression and late promotion stage of mammary gland carcinogenesis in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz(a)anthracene. Cancer Lett., 112, 141--147.
  17. Hibasami,H., Asehiwa,Y., Fujikawa,T. and Komiya,T. (1996) Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds. Anticancer Res., 16, 1943--1946.
  18. Achiwa,Y., Hibasami,H., Katsuzaki,H., Imai,K. and Komiya,T. (1997) Inhibitory effects of persimmon (Diospyros kaki) extract and related polyphenol compounds on growth of human lymphoid leukemia cells. Biosci. Biotechnol. Biochem., 61, 1099--1101.
  19. Okabe,S., Ochiai,Y., Aida,M., Park,K., Kim,S.J., Nomura,T., Suganuma,M. and Fujiki,H. (1997) Mechanisms of growth inhibition of human lung cancer cell line PC-9 by tea polyphenols. Jpn. J. Cancer Res., 88, 639--643.
  20. Suganuma,M., Okabe,S., Kai,Y., Sueoka,N., Sueoka,E. and Fujiki,H. (1999) Synergistic effects of (_)-epigallocatechin gallate with (_)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in the human lung cancer cell line PC-9. Cancer Res., 59, 44--47.
  21. Yang, G.Y., Liao, J., Kim, K., Yurkow, E.J. and Yang, C.S. (1998) Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis, 19, 611--616.
  22. Lyn-Cook, B.D., Rogers, T., Yan, Y., Blann, E.B., Kadlubar, F.F. and Hammons, G.J. (1999) Chemopreventive effects of tea extracts and various components on human pancreatic and prostate cancer cells in vitro. Nutr. Cancer, 35, 80--86.
  23. Takada,M., Nakamura,Y., Koizumi,T., Toyana,H., Kamigaki,T., Suzuki,Y., Takeyama,Y. and Kuroda,Y. (2002) Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate. Pancreas, 25, 45--48.
  24. Basu, A. and Haldar, S. (2003) Identification of a novel Bcl-xL phosphorylation site regulating the sensitivity of taxol- or 2-methoxyestradiolinduced apoptosis. FEBS Lett., 538, 41--47.
  25. Basu, A., Das, M., Qanungo, S., Fan X.-J., DuBois, G. and Haldar, S. (2002) Proteasomal degradation of human peptidyl prolyl isomerase pin1-pointing phospho Bcl2 toward dephosphorylation. Neoplasia, 4, 218--227.
  26. Smiley,S.T., Reers,M., Mottola-Hartshorn,C., Lin,M., Chen,A., Smith,T.W., Steele,G.D.Jr and Chen, L.B. (1991) Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc. Natl Acad. Sci. USA, 88, 3671--3675.
  27. Yethon, J.A., Epand, R.F., Leber, B., Epand, R.M. and Andrews, D.W. (2003) Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis. J. Biol. Chem. 278, 48935--48941.
  28. Qanungo,S., Haldar,S. and Basu,A. (2003) Restoration of silencedPeutz--Jeghers syndrome gene, LKB1, induces apoptosis in pancreatic carcinoma cells. Neoplasia, 5, 367--374.
  29. Soengas, M.S., Alarcon, R.M., Yoshida, H., Giaccia, A.J., Hakem, R., Mak, T.W. and Lowe, S.W. (1999) Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science, 284, 156--159.
  30. Kahn, P. and Shin, S.I. (1979) Cellular tumorigenicity in nude mice. Test of associations among loss of cell-surface fibronectin, anchorage independence, and tumor-forming ability. J. Cell Biol., 82, 1--16.
  31. Haldar, S., Jena, N. and Croce, C.M. (1995) Inactivation of Bcl2 by phosphorylation. Proc. Natl Acad. Sci. USA 92, 4507--4511.
  32. Salvioli,S., Ardizzoni,A., Franceschi,C. and Cossarizza,A. (1997) JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett., 411, 77--82.
  33. Mancini, M., Anderson, B.O., Caldwell, E., Sedghinasab, M., Paty, P.B. and Hockenbery, D.M. (1997) Mitochondrial proliferation and paradoxical membrane depolarization during terminal differentiation and apoptosis in a human colon carcinoma cell line. J. Cell Biol, 138, 449--469.
  34. Zamzami, N. and Kroemer, G. (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat. Rev. Mol. Cell. Biol., 2, 67--71.
  35. Green, D.R., and Reed, J.C. (1998) Mitochondria and apoptosis. Science, 281, 1309--1312.
  36. Li,P., Nijhawan,D., Budihardjo,I., Srinivasula,S.M., Ahmad,M., Alnemri,E.S. and Wang,X. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91, 479--489.
  37. Gewies, A., Rokhlin, O.W. and Cohen, M.B. (2000) Cytochrome c is involved in Fas-mediated apoptosis of prostatic carcinoma cell lines. Cancer Res., 60, 2163--2168.
  38. Wu H, Xin Y, Xu C, Xiao Y. Capecitabine combined with (-)-epigallocatechin 3-gallate inhibits angiogenesis and tumor growth in nude mice with gastric cancer xenografts. Exp Ther Med 2012;3:650–4.
  39. Lee SH, Nam HJ, Kang HJ, Kwon HW, Lim YC. Epigallocatechin-3-gallate attenuates head and neck cancer stem cell traits through suppression of Notch pathway. Eur J Cancer 2013;49:3210–8.
  40. Wu H, Xin Y, Xiao Y, Zhao J. Low-dose docetaxel combined with (-)- epigallocatechin-3-gallate inhibits angiogenesis and tumor growth in nude mice with gastric cancer xenografts. Cancer Biother Radiopharm 2012;27:204–9.
  41. Stearns ME, Amatangelo MD, Varma D, Sell C, Goodyear SM. Combination therapy with epigallocatechin-3-gallate and doxorubicin in human prostate tumor modeling studies: inhibition of metastatic tumor growth in severe combined immunodeficiency mice. Am J Pathol 2010;177:3169–79.
  42. Zhang Y, Wang SX, Ma JW, Li HY, Ye JC, Xie SM, et al. EGCG inhibits properties of glioma stem-like cells and synergizes with temozolomide through downregulation of P-glycoprotein inhibition. J Neurooncol 2015;121:41–52.
  43. Saldanha SN, Kala R, Tollefsbol TO. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate. Exp Cell Res 2014;324:40–53.
  44. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Anti-tumor effect of ascorbic acid, lysine, proline, arginine, and epigallocatechin gallate on prostate cancer cell lines PC-3, LNCaP, and DU145. Res Commun Mol Pathol Pharmacol 2004;115–116:251–64.
  45. Zhou DH, Wang X, Yang M, Shi X, Huang W, Feng Q. Combination of low concentration of (-)-epigallocatechin gallate (EGCG) and curcumin strongly suppress the growth of non-small cell lung cancer in vitro and in vivo through causing cell cycle arrest. Int J Mol Sci 2013;14:12023–36.
  46. Papi A, Farabegoli F, Iori R, Orlandi M, De Nicola GR, Bagatta M, et al. Vitexin-2-O-xyloside, raphasatin and (-)-epigallocatechin-3-gallate synergistically affect cell growth and apoptosis of colon cancer cells. Food Chem 2013;138:1521–30.
  47. Hagen RM, Chedea VS, Mintoff CP, Bowler E, Morse HR, Ladomery MR. Epigallocatechin-3-gallate promotes apoptosis and expression of the caspase 9a splice variant in PC3 prostate cancer cells. Int J Oncol 2013;43:194–200.
  48. Shankar S, Suthakar G, Srivastava RK. Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front Biosci 2007;12:5039–51.
  49. Sanna V, Singh CK, Jashari R, Adhami VM, Chamcheu JC, Rady I, et al. Targeted nanoparticles encapsulating (-)-epigallocatechin-3-gallate for prostate cancer prevention and therapy. Sci Rep 2017;7:41573.
  50. Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 2010;11:621–32.
Make sure you submit a unique essay

Our writers will provide you with an essay sample written from scratch: any topic, any deadline, any instructions.

Cite this Page

Discursive Essay on Antiproliferative Action of EGCG on Pancreatic Cancer Cells. (2022, September 27). Edubirdie. Retrieved December 5, 2023, from
“Discursive Essay on Antiproliferative Action of EGCG on Pancreatic Cancer Cells.” Edubirdie, 27 Sept. 2022,
Discursive Essay on Antiproliferative Action of EGCG on Pancreatic Cancer Cells. [online]. Available at: <> [Accessed 5 Dec. 2023].
Discursive Essay on Antiproliferative Action of EGCG on Pancreatic Cancer Cells [Internet]. Edubirdie. 2022 Sept 27 [cited 2023 Dec 5]. Available from:
Join 100k satisfied students
  • Get original paper written according to your instructions
  • Save time for what matters most
hire writer

Fair Use Policy

EduBirdie considers academic integrity to be the essential part of the learning process and does not support any violation of the academic standards. Should you have any questions regarding our Fair Use Policy or become aware of any violations, please do not hesitate to contact us via

Check it out!
search Stuck on your essay?

We are here 24/7 to write your paper in as fast as 3 hours.