Roy Madhumita, Chakrabarty Sutapa, Sinha Dona, Bhattacharya Rathin Kumar, Siddiqi Maqsood
Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37 SP Mukherjee Road, Kolkata 700 026, India.
Mutat Res. 2003 Feb-Mar;523-524:33-41. doi: 10.1016/s0027-5107(02)00319-6.
Modulation of events characteristic of carcinogenesis or of cancer cells is being emphasized as a rational strategy to control cancer. Green tea polyphenol epigallocatechin gallate (EGCG) has been shown to be highly active as a cancer chemopreventive agent. Certain cellular and molecular events relevant to carcinogenesis are also modified by EGCG. The present investigation was carried out to examine the effects of EGCG on the cytogenetic change and DNA damage induced by toxicant H(2)O(2) and carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Chinese hamster V-79 cells in culture. Cytogenetic change as evident by the formation of micronuclei and DNA damage in the form of comet tail length during single cell gel electrophoresis was found to be significantly suppressed by EGCG in a dose dependent manner. Cells preincubated with EGCG were protected from subsequent damage by the genotoxic agents. Apoptosis, a highly organized physiological mechanism to eliminate injured or abnormal cells, is also implicated in multistage carcinogenesis. Initiated cells, cells at promotional stage or fully transformed cells can be eliminated through apoptosis. It was observed that EGCG suppressed growth and proliferation of K-562 cells derived from human chronic myelogenic leukemia. Morphological features of treated cells and characteristic DNA fragmentation revealed that the cytotoxicity was due to induction of apoptosis. This was mediated by activation of caspase 3 and caspase 8. Results show that EGCG not only protects normal cells against genotoxic hazard but also eliminate cancer cells through induction of apoptosis.
调节致癌过程或癌细胞的特征性事件正被视为一种控制癌症的合理策略。绿茶多酚表没食子儿茶素没食子酸酯(EGCG)已被证明作为一种癌症化学预防剂具有高度活性。与致癌作用相关的某些细胞和分子事件也会被EGCG改变。本研究旨在检测EGCG对培养的中国仓鼠V - 79细胞中由毒物H₂O₂和致癌物N - 甲基 - N'- 硝基 - N - 亚硝基胍(MNNG)诱导的细胞遗传学变化和DNA损伤的影响。结果发现,EGCG以剂量依赖性方式显著抑制了单细胞凝胶电泳中微核形成所显示的细胞遗传学变化以及彗星尾长形式的DNA损伤。预先用EGCG孵育的细胞受到了遗传毒性剂后续损伤的保护。凋亡是一种高度有序的生理机制,用于消除受损或异常细胞,也与多阶段致癌作用有关。起始细胞、促癌阶段的细胞或完全转化的细胞都可以通过凋亡被清除。据观察,EGCG抑制了源自人类慢性粒细胞白血病的K - 562细胞的生长和增殖。处理后细胞的形态特征和特征性DNA片段化表明,细胞毒性是由凋亡诱导引起的。这是由半胱天冬酶3和半胱天冬酶8的激活介导的。结果表明,EGCG不仅能保护正常细胞免受遗传毒性危害,还能通过诱导凋亡消除癌细胞。