Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line
Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line
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DOI：
10.1080/01635589809514701
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发表时间：
1998-01-01
影响因子：
2.9
通讯作者：
Sarkar, FH
中科院分区：
文献类型：
--
作者：
Lian, FR;Bhuiyan, M;Sarkar, FH
肺癌是世界上癌症相关死亡的主要原因，在许多发达国家发病率不断上升。流行病学数据表明，食用豆制品（异黄酮染料木素）可能与降低患乳腺癌和前列腺癌的风险有关；然而，这类研究并不适用于肺癌。我们研究了染料木素对H460非小肺癌细胞的细胞生长抑制、基因表达调节和凋亡诱导。染料木素抑制H460细胞生长呈剂量依赖性。流式细胞分析显示，30 μ M染料木素使细胞周期进程阻滞在G(2)-M期。采用4,6-二氨基-2-苯基吲哚染色、流式细胞术分析和DNA阶梯法观察凋亡细胞的死亡情况，结果表明30 μ M染料木素可引起典型的DNA阶梯，这是细胞凋亡的标志。流式细胞术和4,6-二氨基-2-苯基吲哚染色显示染料木黄酮诱导细胞凋亡。我们的研究还通过Western blot分析了用30和50 μ M染料木素处理24、48和72小时的培养细胞的细胞裂解物对p21（WAF1）的调节。同时免疫细胞化学染色检测p21（WAF1）蛋白的表达。本研究结果显示染料木素可以上调染料木素处理细胞中p21（WAF1）的表达。根据这些结果，我们认为染料木素可能具有抗癌作用，进一步的研究可能会证明其对非小肺癌细胞的作用。因此染料木素的生物学效应可能是由于细胞生长、细胞死亡和细胞周期调节分子的调节。
Lung cancer is the leading cause of cancer-related death in the world, with increasing incidence in many developed countries. Epidemiological data suggest that consumption of soy products (the isoflavone genistein) may be associated with a decreased risk of breast and prostate cancer; however, such studies are not available for lung cancer. We investigated cell growth inhibition, modulation in gene expression, and induction of apoptosis by genistein in H460 non-small lung cancer cells. Genistein inhibited H460 cell growth in a dose-dependent manner. Flow-cytometric analysis showed that 30 mu M genistein arrested cell cycle progression at the G(2)-M phase. 4,6-Diamidino-2-phenylindole staining, flow-cytometric analysis, and DNA laddering were used to investigate apoptotic cell death, and the results show that 30 mu M genistein can cause typical DNA laddering, a hallmark for apoptosis. In addition, flow cytometry and 4,6-diamidino-2-phenylindole staining showed induction of apoptosis by genistein. Our investigation also demonstrated the modulation of p21(WAF1) by Western blot analysis of cell lysates obtained from cultured cells treated with 30 and 50 mu M genistein for 24, 48, and 72 hours. Simultaneously, immunocytochemical staining was conducted for the expression of p21(WAF1) protein. Our results showed that genistein can upregulate p21(WAF1) expression in genistein-treated cells. From these results, we conclude that genistein may act as an anticancer agent, and further studies may prove its efficacy in non-small lung cancer cells. Thus the biological effects of genistein may, indeed, be due to the modulation of cell growth, cell death, and cell cycle regulatory molecules.