Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest.
Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest.
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染料木黄酮抑制辐射诱导的NF-kappab在促进凋亡和G2/M细胞周期停滞的前列腺癌细胞中的激活。
DOI：
10.1186/1471-2407-6-107
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发表时间：
2006-04-26
期刊：
影响因子：
3.8
通讯作者：
Hillman, Gilda G.
中科院分区：
文献类型：
--
作者：
Raffoul, Julian J.;Wang, Yu;Kucuk, Omer;Forman, Jeffrey D.;Sarkar, Fazlul H.;Hillman, Gilda G.
必须研究新的癌症治疗策略，以增强前列腺癌的治疗，同时最大限度地减少相关的毒性。我们之前已经证明，大豆中发现的主要异黄酮金雀异黄酮可以在体外和体内增强前列腺癌的放射治疗。在这项研究中，我们使用 PC-3 人类前列腺癌细胞研究了金雀异黄素与辐射之间的细胞和分子相互作用。通过克隆形成分析、流式细胞术、NF-κB 的 EMSA 分析以及细胞周期蛋白 B1、p21WAF1/Cip1 和切割的 PARP 蛋白的蛋白质印迹分析来确定肿瘤细胞的存活和进展。与单独使用金雀异黄素或放射线相比，金雀异黄素与放射线结合对 PC-3 集落形成产生更大的抑制作用。金雀异黄素的治疗顺序随后是放射和持续暴露于金雀异黄酮，显示出最佳效果。细胞周期分析表明金雀异黄素和辐射诱导的显着剂量和时间依赖性 G2/M 停滞与 p21WAF1/Cip1 表达增加和细胞周期蛋白 B1 表达减少相关。金雀异黄素显着降低 NF-κB 活性，但辐射却增加了 NF-κB 活性。金雀异黄素预处理强烈抑制辐射诱导的 NF-κB 活性激活。在金雀异黄素和放射治疗联合治疗后，测量到裂解的 PARP 蛋白显着且惊人的增加，表明细胞凋亡增加。金雀异黄素和辐射增加细胞死亡的机制被认为是通过抑制 NF-κB 发生的，导致调节细胞周期蛋白（如细胞周期蛋白 B 和/或 p21WAF1/Cip1）的表达改变，从而促进 G2/M 停滞并增加放射敏感性。这些发现支持金雀异黄素与放射治疗相结合来治疗前列腺癌的重要且新颖的策略。
New cancer therapeutic strategies must be investigated that enhance prostate cancer treatment while minimizing associated toxicities. We have previously shown that genistein, the major isoflavone found in soy, enhanced prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated the cellular and molecular interaction between genistein and radiation using PC-3 human prostate cancer cells. Tumor cell survival and progression was determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-κB, and western blot analysis of cyclin B1, p21WAF1/Cip1, and cleaved PARP protein. Genistein combined with radiation caused greater inhibition in PC-3 colony formation compared to genistein or radiation alone. Treatment sequence of genistein followed by radiation and continuous exposure to genistein showed optimal effect. Cell cycle analysis demonstrated a significant dose- and time-dependent G2/M arrest induced by genistein and radiation that correlated with increased p21WAF1/Cip1 and decreased cyclin B1 expression. NF-κB activity was significantly decreased by genistein, yet increased by radiation. Radiation-induced activation of NF-κB activity was strongly inhibited by genistein pre-treatment. A significant and striking increase in cleaved PARP protein was measured following combined genistein and radiation treatment, indicating increased apoptosis. A mechanism of increased cell death by genistein and radiation is proposed to occur via inhibition of NF-κB, leading to altered expression of regulatory cell cycle proteins such as cyclin B and/or p21WAF1/Cip1, thus promoting G2/M arrest and increased radiosensitivity. These findings support the important and novel strategy of combining genistein with radiation for the treatment of prostate cancer.
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影响因子：
6.2
作者：
GIOVANNUCCI, E
通讯作者：
GIOVANNUCCI, E
影响因子：
2.9
作者：
Li, YW;Ellis, KL;Sarkar, FH
通讯作者：
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影响因子：
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作者：
Mohammad, RM;Banerjee, S;Sarkar, FH
通讯作者：
Sarkar, FH
影响因子：
2.9
作者：
Alhasan, SA;Pietrasczkiwicz, H;Sarkar, FH
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在PC-3人前列腺癌细胞系中染料木黄酮的实验性抗溶酶抑制剂SB715992的治疗潜力增加。
影响因子：
3.8
作者：
Davis, DA;Sarkar, SH;Hussain, M;Li, YW;Sarkar, FH
通讯作者：
Sarkar, FH