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. 2013 Dec 13;30(1):67–73. doi: 10.1007/s12264-013-1394-z

Epigallocatechin-3-gallate induces apoptosis, inhibits proliferation and decreases invasion of glioma cell

Hong Li 1, Zhe Li 1, Ya-Ming Xu 1, Yue Wu 1, Kang-Kang Yu 1, Can Zhang 1, Yong-Hua Ji 1, Gang Ding 2,✉, Fu-Xue Chen 1,✉
PMCID: PMC5562579  PMID: 24338484

Abstract

Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has been considered a potential therapeutic and chemopreventive agent for cancer. Glioma is a malignant tumor with high mortality but effective therapy has not yet been developed. In this study, we found that EGCG induced apoptosis in U251 glioma cells via the laminin receptor (molecular weight 67kDa) in a time- and dose-dependent manner, decreased their invasiveness and inhibited their proliferation. The mitogen-activated protein kinase pathway was shown to be involved in glioma cell apoptosis and proliferation. Furthermore, the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9 were reduced after EGCG treatment. These results suggest that EGCG has important therapeutic effects with low toxicity and side-effects, and could be used in cancer chemoprevention.

Keywords: glioma, epigallocatechin-3-gallate, proliferation, apoptosis, invasion

Footnotes

These authors contributed equally to this work.

Contributor Information

Gang Ding, Email: ddinggang@hotmail.com.

Fu-Xue Chen, Email: chenfuxue@staff.shu.edu.cn.

References

  • [1].Lisa M, DeAngelis MD. Brain tumors. N Engl J Med. 2001;344:114–123. doi: 10.1056/NEJM200101113440207. [DOI] [PubMed] [Google Scholar]
  • [2].Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annu Rev Neurosci. 2001;24:385–428. doi: 10.1146/annurev.neuro.24.1.385. [DOI] [PubMed] [Google Scholar]
  • [3].Louis D O, Wiestler OD, Cavenee WK, Burger PC, Jouvet A. The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol. 2007;114:97–109. doi: 10.1007/s00401-007-0243-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–760. doi: 10.1038/nature05236. [DOI] [PubMed] [Google Scholar]
  • [5].Curran WJ, Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, et al. Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst. 1993;85:704–710. doi: 10.1093/jnci/85.9.704. [DOI] [PubMed] [Google Scholar]
  • [6].Khan N, Mukhtar H. Tea polyphenols for health promotion. Life Sci. 2007;81:519–533. doi: 10.1016/j.lfs.2007.06.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Siddiqui IA, Shukla Y, Adhami VM, Sarfaraz S, Asim M, Hafeez BB, et al. Suppression of NFkappaB and its regulated gene products by oral administration of green tea polyphenols in an autochthonous mouse prostate cancer model. Pharm Res. 2008;25:2135–2142. doi: 10.1007/s11095-008-9553-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Lesot H, Kühl U, Mark K. Isolation of a laminin-binding protein from muscle cell membranes. EMBO J. 1983;2:861–865. doi: 10.1002/j.1460-2075.1983.tb01514.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Malinoff HL, Wicha MS. Isolation of a cell surface receptor protein for laminin from murine fibrosarcoma cells. J Cell Biol. 1983;96:1475–1479. doi: 10.1083/jcb.96.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Rao NC, Barsky SH, Terranova VP, Liotta LA. Isolation of a tumor cell laminin receptor. Biochem Biophys Res Commun. 1983;111:804–808. doi: 10.1016/0006-291X(83)91370-0. [DOI] [PubMed] [Google Scholar]
  • [11].Yang Y, Qiu Y, Ren W, Gong J, Chen F. An identification of stem cell-resembling gene expression profiles in high-grade astrocytomas. Mol Carcinog. 2008;47:893–903. doi: 10.1002/mc.20443. [DOI] [PubMed] [Google Scholar]
  • [12].Chen FX, Qian YR, Duan YH, Ren WW, Yang Y, Zhang CC, et al. Down-regulation of 67LR reduces the migratory activity of human glioma cells in vitro. Brain Res Bull. 2009;79:402–408. doi: 10.1016/j.brainresbull.2009.04.019. [DOI] [PubMed] [Google Scholar]
  • [13].Sylvie Ménard ETaMC. The 67 kDa laminin receptor as a prognostic factor in human cancer. Breast Cancer Res Treat. 1983;52:137–145. doi: 10.1023/a:1006171403765. [DOI] [PubMed] [Google Scholar]
  • [14].Boukerche H, Su ZZ, Kang DC, Fisher PB. Identification and cloning of genes displaying elevated expression as a consequence of metastatic progression in human melanoma cells by rapid subtraction hybridisation. Gene. 2004;343:191–201. doi: 10.1016/j.gene.2004.09.002. [DOI] [PubMed] [Google Scholar]
  • [15].Alberts AS. Identification of a carboxyl-terminal diaphanousrelated formin homology protein autoregulatory domain. J Bio Chem. 2001;276:2824–2830. doi: 10.1074/jbc.M006205200. [DOI] [PubMed] [Google Scholar]
  • [16].Tachibana H, Koga K, Fujimura Y, Yamada K. A receptor for green tea polyphenol EGCG. Nat Struct Mol Biol. 2004;11:380–381. doi: 10.1038/nsmb743. [DOI] [PubMed] [Google Scholar]
  • [17].Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–174. doi: 10.1038/nrc745. [DOI] [PubMed] [Google Scholar]
  • [18].Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 2006;25:9–34. doi: 10.1007/s10555-006-7886-9. [DOI] [PubMed] [Google Scholar]
  • [19].Overall CM, Kleifeld O. Tumour microenvironment — opinion: validating matrix metalloproteinases as drug targets and antitargets for cancer therapy. Nat Rev Cancer. 2006;6:227–239. doi: 10.1038/nrc1821. [DOI] [PubMed] [Google Scholar]
  • [20].Siegelin M, Habel A, Gaiser T. Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma. Neurosci Lett. 2008;448:161–165. doi: 10.1016/j.neulet.2008.10.036. [DOI] [PubMed] [Google Scholar]
  • [21].Choi YJ, Lim SY, Woo JH, Kim YH, Kwon YK, Suh SI, et al. Sodium orthovanadate potentiates EGCG-induced apoptosis that is dependent on the ERK pathway. Biochem Biophys Res Commun. 2003;305:176–185. doi: 10.1016/S0006-291X(03)00719-8. [DOI] [PubMed] [Google Scholar]
  • [22].Ahmad N F, 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. 1997;89:1881–1886. doi: 10.1093/jnci/89.24.1881. [DOI] [PubMed] [Google Scholar]
  • [23].Rao SD, Pagidas K. Epigallocatechin-3-gallate, a natural polyphenol, inhibits cell proliferation and induces apoptosis in human ovarian cancer cells. Anticancer Res. 2010;30:2519–2523. [PubMed] [Google Scholar]
  • [24].Thangapazham RL, Passi N, Maheshwari RK. Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells. Cancer Biol Ther. 2007;6:1938–1943. doi: 10.4161/cbt.6.12.4974. [DOI] [PubMed] [Google Scholar]
  • [25].Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavencc WK, et al. Malignant glioma: Genetics and biology of a grave matter. Genes Dev. 2001;15:1311–1333. doi: 10.1101/gad.891601. [DOI] [PubMed] [Google Scholar]
  • [26].Gao Y, Li W, Jia L, Li B, Chen YC, Tu Y. Enhancement of (−)-epigallocatechin-3-gallate and theaflavin-3-3′-digallate induced apoptosis by ascorbic acid in human lung adenocarcinoma SPCA-1 cells and esophageal carcinoma Eca-109 cells via MAPK pathways. Biochem Biophys Res Commun. 2013;438:370–374. doi: 10.1016/j.bbrc.2013.07.078. [DOI] [PubMed] [Google Scholar]
  • [27].Garzetti G C, Lucarini G, Goteri G, De Nicolis M, Garbisa S, Masiero L, et al. Tissue and serum metalloproteinase (MMP-2) expression in advanced ovarianserous cytstadenocarcinomas: clinical and prognostic implications. Anticancer Res. 1995;15:2799–2804. [PubMed] [Google Scholar]
  • [28].Stetler-Stevenson WG. The role of matrix metalloproteinases in tumor invasion, metastasis and angiogenesis. Surg Oncol Clin NAm. 2001;10:383–392. [PubMed] [Google Scholar]
  • [29].Gohji K, Fujimoto N, Hara I, Fujii A, Gotoh A, Okada H, et al. Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension. Int J Cancer. 1998;79:96–101. doi: 10.1002/(SICI)1097-0215(19980220)79:1<96::AID-IJC18>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  • [30].Blazquez C, Salazar M, Carracedo A, Lorente M, Egia A, Gonzalez-Feria L, et al. Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression. Cancer Res. 2008;68:1945–1952. doi: 10.1158/0008-5472.CAN-07-5176. [DOI] [PubMed] [Google Scholar]

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