Synergistic effect of green tea catechins on cell growth and apoptosis induction in gastric carcinoma cells
Synergistic effect of green tea catechins on cell growth and apoptosis induction in gastric carcinoma cells
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DOI：
10.1248/bpb.28.574
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发表时间：
2005-04-01
影响因子：
2
通讯作者：
Takeishi, K
中科院分区：
文献类型：
--
作者：
Horie, N;Hirabayashi, N;Takeishi, K
（-）-表没食子儿茶素没食子酸酯（EGCG）是绿茶儿茶素的主要成分，已知在多种培养细胞中抑制细胞生长并诱导细胞凋亡。我们研究了绿茶儿茶素对人胃癌细胞的影响。EGCG对四种细胞系（MKN-1、MKN-45、MKN74和KATO-III）的增殖呈剂量依赖性抑制。四种细胞系中，对MKN-45细胞的生长抑制效果最好（IC50: 40 μ m EGCG），而对KATO-III细胞的生长不敏感（IC50: 80 ~ 150 μ m）。此外，(-)-表儿茶素（EC）对EGCG处理的MKN-45细胞的凋亡诱导具有主要的协同作用；但对EGCG诱导的细胞生长抑制作用不明显。为了研究EGCG诱导凋亡的分子机制，我们检测了EGCG处理的MKN-45细胞中caspase的活性。在EGCG处理的细胞中，caspase -3、-8和-9的活性水平升高，表明这些caspase参与了EGCG诱导的细胞凋亡。此外，EC与EGCG诱导凋亡的协同作用被过氧化氢酶处理特异性地取消，这表明这种协同作用涉及细胞外活性氧的产生。
(-)-Epigallocatechin gallate (EGCG), a major component of green tea catechins, is known to inhibit cell growth and to induce apoptosis in a variety of cultured cells. We examined effects of green tea catechins in cultured cells derived from human gastric carcinoma. The proliferation of four cell lines (MKN-1, MKN-45, MKN74 and KATO-III) was inhibited with EGCG in a dose-dependent manner. The growth of MKN-45 cells was most efficiently inhibited by the treatment (IC50: 40 mu m EGCG) among the four cell lines, while KATO-III cells were most insensitive (IC50: 80-150 mu m) to the EGCG treatment. In addition, (-)-epicatechin (EC) had a major synergistic effect on the induction of apoptosis in MKN-45 cells treated with EGCG; however it had little effect on the inhibition of cell growth induced by EGCG. To study the molecular mechanisms behind the induction of apoptosis by EGCG, the activity of caspases in MKN-45 cells treated with EGCG was examined. Activity levels of caspases-3, -8 and -9 were elevated in EGCG-treated cells, suggesting that these caspases are involved in the apoptosis induced by EGCG. Furthermore, the synergistic effect of EC with EGCG on the induction of apoptosis was specifically canceled by catalase treatment, suggesting that the synergism involves the extracellular production of reactive oxygen species.