Epigallocatechin-3-gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility
Epigallocatechin-3-gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility
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DOI：
10.1002/jcp.20569
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发表时间：
2006-05-01
影响因子：
5.6
通讯作者：
Fong, D
中科院分区：
文献类型：
--
作者：
Chan, MM;Soprano, KJ;Fong, D
绿茶多酚表没食子儿茶素没食子酸酯(EGCG)对多种癌症具有化学预防作用。众所周知，这种化合物可以攻击转化细胞中的各种目标。在这篇报道中，我们研究了EGCG对卵巢癌细胞的作用。对8种卵巢癌细胞株(SKOV3、CAOV3、OVCAR3、OVCAR10、A2780、CP70、C30和C200)进行了检测，发现S对EGCG的IC(50)在微摩尔范围内，包括对化疗药物顺铂耐药的细胞。卵巢癌细胞对相似浓度的过氧化氢敏感，EGCG处理后细胞内过氧化氢浓度升高。与过氧化氢的清除剂丙酮酸的中和表明，EGCG的毒性可能是通过自由基的氧化应激来介导的。超氧化物歧化酶模拟物Tempoll的加入表明，过氧化氢可能是由超氧化物内源产生的。顺铂的毒性和顺铂耐药性的产生是卵巢癌治疗的主要障碍。我们发现EGCG的加入放大了顺铂的毒性。EGCG使SKOV3、CAOV3和C200细胞对顺铂的耐药性增加了三到六倍，后者是一种诱导对顺铂具有数百倍抗药性的细胞株。我们的发现表明，EGCG可能会加重氧化应激，抑制卵巢癌细胞的生长，并使其对顺铂敏感。
The green tea polyphenol epigallocatechin-3-gallate (EGCG) has cancer chemopreventive properties against various types of cancers. The compound is known to attack various targets in transformed cells. In this report, we examined the action of EGCG on ovarian cancer cells. Eight ovarian cancer cell lines were tested (SKOV3, CAOV3, OVCAR3, OVCAR10, A2780, CP70, C30, and C200) and showed IC(50)s for EGCG at the micromolar range, including ones that are resistant to the chemotherapeutic drug cisplatin. The ovarian cancer cells were sensitive to H2O2 at similar concentrations, and EGCG treatment led to enhanced intracellular H2O2. Neutralization with pyruvate, a scavenger of H2O2, Suggests that the toxicity of EGCG may be mediated by oxidative stress from the free radical. Addition of Tempol, a Superoxide dismutase mimetic, demonstrates that H2O2 might begenerated endogenously from superoxide. The toxicity of cisplatin and the development of cisplatin resistance are major obstacles in treatment of ovarian cancer. We found that addition of EGCG amplified the toxicity of cisplatin. EGCG increased cisplatin potency by three to six-fold ill SKOV3, CAOV3, and C200 cells, the latter being a cell line induced to have several hundred fold resistant to cisplatin above the parental line. Our findings suggest that EGCG may accentuate oxidative stress to inhibit growth of ovarian cancer cells and sensitize them to cisplatin.