Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression
Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression
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DOI：
10.1016/j.canep.2012.07.005
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发表时间：
2012-12-01
影响因子：
2.6
通讯作者：
Sharma, Chhavi
中科院分区：
文献类型：
--
作者：
Hussain, Arif;Harish, Geetganga;Sharma, Chhavi
背景资料：癌症治疗的最具挑战性的绊脚石之一是癌细胞能够打破天然屏障并从其起源部位扩散到非相邻区域和远处部位，这是癌症死亡率高的原因。Gamut实验和流行病学数据提倡使用药物或营养干预来抑制或延迟癌症的各个阶段，如侵袭和转移。方法：采用细胞活力测定法研究染料木黄酮对HeLa细胞的细胞毒作用，并通过细胞核形态学观察、DNA梯状条带分析和细胞周期分析等方法研究染料木黄酮诱导HeLa细胞死亡的方式。此外，为了确定其对HeLa细胞迁移的抑制作用，进行了划痕实验，这些结果与参与侵袭和迁移的基因表达相关RT-PCR检测MMP-9和TIMP-1的表达。HeLa细胞暴露于染料木黄酮导致显著的剂量和时间依赖性生长抑制，细胞周期阻滞于G（2）/M期，细胞凋亡是其介导的机制。结论：金雀异黄素可能是一种有效的抗肿瘤药物，可抑制肿瘤细胞的生长和侵袭转移。因此，可以开发利用染料木黄酮的治疗策略以显著降低癌症发病率和死亡率。(C)2012爱思唯尔有限公司保留所有权利。
Background: One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibit or delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities.Methods: In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR.Results: The exposure of HeLa cells to genistein resulted in significant dose-and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G(2)/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1.Conclusion: Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality. (C) 2012 Elsevier Ltd. All rights reserved.