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(-)-Epigallocatechin-3-Gallate Induces Apoptosis and Inhibits Invasion and Migration of Human Cervical Cancer Cells

  • Sharma, Chhavi (Department of Biotechnology, Manipal University) ;
  • Nusri, Qurrat El-Ain (Department of Biotechnology, Manipal University) ;
  • Begum, Salema (Department of Biotechnology, Manipal University) ;
  • Javed, Elham (Department of Biotechnology, Manipal University) ;
  • Rizvi, Tahir A. (Department of Microbiology and Immunology, Faculty of Medicine and Health Science, UAE University) ;
  • Hussain, Arif (Department of Biotechnology, Manipal University)
  • Published : 2012.09.30

Abstract

Invasion and metastasis are the major causes of cancer-related death. Pharmacological or therapeutic interventions such as chemoprevention of the progression stages of neoplastic development could result in substantial reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent, has attracted extensive interest for cancer therapy utilizing its antioxidant, anti-proliferative and inhibitory effects on angiogenesis and tumor cell invasion. In this study, we assessed the influence of EGCG on the proliferative potential of HeLa cells by cell viability assay and authenticated the results by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Further we analyzed the anti-invasive properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP-1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of HeLa cells in a dose- and time-dependent manner. It was observed that cell death mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited invasion and migration of HeLa cells and modulated the expression of related genes (MMP-9 and TIMP-1). These results indicate that EGCG may effectively suppress promotion and progression stages of cervical cancer development.

Keywords

References

  1. Agarwal C, Sharma Y, Agarwal R (2000). Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells. modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis. Mol Carcinog, 28, 129-38. https://doi.org/10.1002/1098-2744(200007)28:3<129::AID-MC1>3.0.CO;2-0
  2. Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H (1997). Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst, 89, 1881-6. https://doi.org/10.1093/jnci/89.24.1881
  3. Artali R, Beretta G, Morazzoni P, Bombardelli E, Meneghetti F (2009). Green tea catechins in chemoprevention of cancer. a molecular docking investigation into their interaction with glutathione S-transferase (GST P1-1). J Enzyme Inhib Med Chem, 24, 287-95. https://doi.org/10.1080/14756360802177282
  4. Aziz MH, Kumar R, Ahmad N (2003). Cancer chemoprevention by resveratrol. In vitro and in vivo studies and the underlying mechanisms. Int J Oncol, 23,17-28.
  5. Baek SM, Kwon CH, Kim JH, et al (2003). Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells. J Lab Clin Med, 142, 178-86. https://doi.org/10.1016/S0022-2143(03)00111-2
  6. Bal DG, Foerster SB, Backman DR, Lyman DO (2001). Dietary change and cancer. challenges and future direction. J Nutr, 131,181-5.
  7. Chan CM, Huang JH, Chiang HS, et al (2010). Effects of (-)-epigallocatechin gallate on RPE cell migration and adhesion. Molecular Vision, 16, 586-95.
  8. Chen JJ, YE Z, Koo MWL (2004). Growth inhibition and cell cycle arrest effects of epigallocatechin gallate in the NBTII bladder tumor cell line. BJU International, 93,1082-6. https://doi.org/10.1111/j.1464-410X.2004.04785.x
  9. Clement MV, Hirpara JL, Chawdhury SH, Pervaiz S (1998). Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood, 92, 996-1002.
  10. D'Agostini F, Izzotti A, Balansky RM, Bennicelli C, De Flora S (2005). Modulation of apoptosis by cancer chemopreventive agents. Mutat Res, 591,173-86. https://doi.org/10.1016/j.mrfmmm.2005.03.034
  11. Duffy MJ, Maguire TM, Hill A, McDermott E, O'Higgins N (2000). Metalloproteinases. role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res, 2, 252-7. https://doi.org/10.1186/bcr65
  12. Farabegoli F, Papi A, Orlandi M (2011). (-)-Epigallocatechin- 3-gallate down-regulates EGFR, MMP-2, MMP-9 and EMMPRIN and inhibits the invasion of MCF-7 tamoxifenresistant cells. Biosci Rep, 31, 99-108. https://doi.org/10.1042/BSR20090143
  13. Giannelli G, Antonaci S (2005). MMP and TIMP assay in cancer. Biological and clinical significance. Int J Cancer, 116, 1002-3. https://doi.org/10.1002/ijc.21128
  14. Gomis-Ruth FX, Maskos K, Betz M, et al (1997). Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Nature, 389, 77-81. https://doi.org/10.1038/37995
  15. Gu B, Ding Q, Xia G, Fang Z (2009). EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. Oncol Rep, 21, 635-40.
  16. Gupta S, Hussain T, Mukhtar H (2003). Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch Biochem Biophys, 410, 177-85. https://doi.org/10.1016/S0003-9861(02)00668-9
  17. Gupta S, Pramanik D, Mukherjee R, et al (2011). Molecular Determinants of Retinoic Acid Sensitivity in Pancreatic Cancer. Clin Cancer Res, 11, 2165.
  18. Harakeh S, Abu-El-Ardat K, Diab-Assaf M, et al (2008). Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in HTLV-1-positive and -negative leukemia cells. Med Oncol, 25,30-9. https://doi.org/10.1007/s12032-007-0036-6
  19. Hibasami H, Achiwa Y, Fujikawa T, Komiya T (1996). Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds. Anticancer Res, 16, 1943-6.
  20. Holten-Andersen MN, Murphy G, Nielsen HJ, et al (1999). Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer. Br J Cancer, 80, 495-503. https://doi.org/10.1038/sj.bjc.6690384
  21. Hsu YC, Liou YM (2011). The anti-cancer effects of (-)-epigallocatechin-3-gallate on the signaling pathways associated with membrane receptors in MCF-7 cells. J Cell Physiol, 226, 2721-30. https://doi.org/10.1002/jcp.22623
  22. Huh SW, Bae SM, Kim YW, et al (2004). Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines. Gynecol Oncol, 94, 760-8. https://doi.org/10.1016/j.ygyno.2004.05.031
  23. Jones JL, Glynn P, Walker RA (1999). Expression of MMP-2 and MMP-9, their inhibitors, and the activator MT1-MMP in primary breast carcinomas. J Pathol, 189, 161-8. https://doi.org/10.1002/(SICI)1096-9896(199910)189:2<161::AID-PATH406>3.0.CO;2-2
  24. Jung YD, Kim MS, Shin BA, et al (2001). EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer, 84, 844-50. https://doi.org/10.1054/bjoc.2000.1691
  25. Kazi A, Smith DM, Zhong Q, Dou QP (2002). Inhibition of Bcl- XL Phosphorylation by Tea Polyphenols or Epigallocatechin- 3-Gallate Is Associated with Prostate Cancer Cell Apoptosis. Mol Pharmacol, 62, 765-71. https://doi.org/10.1124/mol.62.4.765
  26. Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H (2006). Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. Cancer Res, 66, 2500-5. https://doi.org/10.1158/0008-5472.CAN-05-3636
  27. Khuri FR, Kim ES, Lee JJ, et al (2001). The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev, 10, 823-9.
  28. Kim C, Moon S (2005). Epigallocatechin-3-gallate causes the p21/WAF1-mediated G1-phase arrest of cell cycle and inhibits matrix metalloproteinase-9 expression in TNF- ${\alpha}$-induced vascular smooth muscle cells. Arch Biochem Biophy, 435, 264-72. https://doi.org/10.1016/j.abb.2004.12.022
  29. Kim HS, Kim MH, Jeong M, et al (2004). EGCG Blocks Tumor Promoter-induced MMP-9 Expression Via Suppression of MAPK and AP-1 Activation in Human Gastric AGS Cells. Anticancer Res, 24, 747-54.
  30. Lambert E, Dasse E, Haye B, Petitfrere E (2004). TIMPs as multifacial proteins. Crit Rev Oncol Hematol, 49, 187-98. https://doi.org/10.1016/j.critrevonc.2003.09.008
  31. Lambert JD, Yang CS (2003). Mechanisms of cancer prevention by tea constituents. J Nutr, 133, 3262-7.
  32. Lee HS, Seo EY, Kang NE, Kim WK (2008). (6)-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells. J Nutr Biochem, 19, 313-9. https://doi.org/10.1016/j.jnutbio.2007.05.008
  33. Li HC, Yashiki S, Sonoda J, et al (2000). Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients. Jpn J Cancer Res, 91, 34-40. https://doi.org/10.1111/j.1349-7006.2000.tb00857.x
  34. Li Y, Che M, Bhagat S, et al (2004). Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia, 6, 354-63. https://doi.org/10.1593/neo.03478
  35. Liang YC, Lin-Shiau SY, Chen CF, Lin JK (1999). Inhibition of cyclin-dependent kinases 2 and 4 activities as well as induction of Cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (-)-epigallocatechin-3- gallate. J Cell Biochem, 75, 1-12.
  36. Maeda-Yamamoto M, Suzuki N, Sawai Y, et al (2003). Association of suppression of extracellular signal-regulated kinase phosphorylation by epigallocatechin gallate with the reduction of matrix metalloproteinase activities in human fibrosarcoma HT 1080 cells. J Agric Food Chem, 51, 1858-63. https://doi.org/10.1021/jf021039l
  37. Matsuura N, Miyamae Y, Yamane K, et al (2006). Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells. J Nutr, 136, 842-6.
  38. Moongkarndi P, Kosem N, Kaslungka S, et al (2004). Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol, 90, 161-6. https://doi.org/10.1016/j.jep.2003.09.048
  39. Park JH, Yoon JH, Kim SA, Ahn SG, Yoon JH (2010). (-)-Epigallocatechin-3-gallate inhibits invasion and migration of salivary gland adenocarcinoma cells. Oncol Rep, 23, 585-90.
  40. Punathil T, Tollefsbol TO, Katiyar SK (2008). EGCG inhibits cancer cell migration through inhibition of nitric oxide synthase and guanylate cyclise. Biochem Biophys Res Commun, 375, 162-7. https://doi.org/10.1016/j.bbrc.2008.07.157
  41. Qanungo S, Das M, Haldar S, Basu A (2005). Epigallocatechin- 3-gallate induces mitochondrial membrane depolarization and caspase-dependent apoptosis in pancreatic cancer cells. Carcinogenesis, 26, 958-67.
  42. Qi W, Weber CR, Wasland K, Savkovic SD (2011). Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer, 11, 219. https://doi.org/10.1186/1471-2407-11-219
  43. Qiao Y, Cao J, Xie L, Shi X (2009). Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells. Arch Pharm Res, 32, 1309-15. https://doi.org/10.1007/s12272-009-1917-3
  44. Rao SD, Pagidas K (2010). Epigallocatechin-3-gallate, a Natural Polyphenol, Inhibits Cell Proliferation and Induces Apoptosis in Human Ovarian Cancer Cells. Anticancer Res, 30, 2519-24.
  45. Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A (2010). Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines. Oncol Rep, 24, 747-57.
  46. Roy M, Siddiqi M, Bhattacharya RK (2001). Cancer Chemoprevention. Tea Polyphenol Induced Cellular and Molecular Responses. Asian Pac J Cancer Prev, 2, 109-16.
  47. Seeram NP, Henning SM, Niu Y, et al (2006). Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity. J Agric Food Chem, 54, 1599-603. https://doi.org/10.1021/jf052857r
  48. Sen T, Chatterjee A (2011). Epigallocatechin-3-gallate (EGCG) downregulates EGF-induced MMP-9 in breast cancer cells. involvement of integrin receptor ${\alpha}5{\beta}1$ in the process. Eur J Nutr, 50, 465-78. https://doi.org/10.1007/s00394-010-0158-z
  49. Sen T, Dutta A, Chatterjee A (2010). Epigallocatechin-3- gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFkappaB and AP-1 in the human breast cancer cell line MDA-MB-231. Anticancer Drugs, 21, 632-44. https://doi.org/10.1097/CAD.0b013e32833a4385
  50. Shankar S, Ganapathy S, Hingorani SR, Srivastava RK (2008). EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci, 13, 440-52. https://doi.org/10.2741/2691
  51. Sharma C, Kaur J, Shishodia S, Aggarwal BB, Ralhan R (2006). Curcumin down regulates smokeless tobacco-induced NFkappaB activation and COX-2 expression in human oral premalignant and cancer cells. Toxicology, 228, 1-15. https://doi.org/10.1016/j.tox.2006.07.027
  52. Sharma C, Sadrieh L, Priyani A, et al (2011). Anti-carcinogenic effects of sulforaphane in association with its apoptosisinducing and anti-inflammatory properties in human cervical cancer cells. Cancer Epidemiol, 35, 272-8. https://doi.org/10.1016/j.canep.2010.09.008
  53. Shirakami Y, Shimizu M, Adachi S, et al (2009). (-)-Epigallocatechin gallate suppresses the growth of human hepatocellular carcinoma cells by inhibiting activation of the vascular endothelial growth factor-vascular endothelial growth factor receptor axis. Cancer Sci, 100, 1957-62. https://doi.org/10.1111/j.1349-7006.2009.01241.x
  54. Siddiqui IA, Malik A, Adhami VM, et al (2008). Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene, 27, 2055-63. https://doi.org/10.1038/sj.onc.1210840
  55. Sporn MB (1996). The war on cancer. Lancet, 347, 1377-81. https://doi.org/10.1016/S0140-6736(96)91015-6
  56. Sporn MB, Suh N(2000). Chemoprevention of cancer. Carcinogenesis, 21, 525-30. https://doi.org/10.1093/carcin/21.3.525
  57. Stingl JC, Ettrich T, Muche R, et al (2011). Protocol for minimizing the risk of metachronous adenomas of the colorectum with green tea extract (MIRACLE). a randomised controlled trial of green tea extract versus placebo for nutriprevention of metachronous colon adenomas in the elderly population. BMC Cancer, 11, 360. https://doi.org/10.1186/1471-2407-11-360
  58. Takada M, Nakamura Y, Koizumi T, et al (2002). Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate. Pancreas, 25, 45-8. https://doi.org/10.1097/00006676-200207000-00012
  59. Takahashi H, Nomata K, Mori K, et al (2004). The preventive effect of green tea on the gap junction intercellular communication in renal epithelial cells treated with a renal carcinogen. Anticancer Res, 24, 3757-62.
  60. Tang GQ, Yan TQ, Guo W, et al (2010). (-)-Epigallocatechin- 3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells. J Cancer Res Clin Oncol, 136, 1179-85. https://doi.org/10.1007/s00432-010-0765-3
  61. Visse R, Nagase H (2003). Matrix metalloproteinases and tissue inhibitors of metalloproteinases. structure, function, and biochemistry. Circ Res, 92, 827-39. https://doi.org/10.1161/01.RES.0000070112.80711.3D
  62. Wels J, Kaplan RN, Rafii S, Lyden D (2008). Migratory neighbors and distant invaders. tumor-associated niche cells. Genes Dev, 22, 559-74. https://doi.org/10.1101/gad.1636908
  63. Yang CS, Maliakal P, Meng X (2002). Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol, 42, 25-54. https://doi.org/10.1146/annurev.pharmtox.42.082101.154309
  64. Yang G, Liao J, Kim K, Yurkow EJ, Yang CS (1998). Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis, 19, 611-6. https://doi.org/10.1093/carcin/19.4.611
  65. Zaveri NT (2006). Green tea and its polyphenolic catechins. Medicinal uses in cancer and noncancer applications. Life Sciences, 78, 2073-80. https://doi.org/10.1016/j.lfs.2005.12.006
  66. Zhang W, Hashimoto K, Yu GY, Sakagami H (2002). Decline of superoxide dismutase activity during antioxidant-induced apoptosis in HL-60 cells. Anticancer Res, 22, 219-24.
  67. Zhou F, Zhou H, Wang T, et al (2011). Epigallocatechin-3-gallate inhibits proliferation and migration of human colon cancer SW620 cells in vitro. Acta Pharmacol Sin, 10, 139.
  68. Zhu BH, Chen HY, Zhan WH, et al (2011). (-)-Epigallocatechin- 3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer. World J Gastroenterol, 17, 2315-25. https://doi.org/10.3748/wjg.v17.i18.2315

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