Vitexicarpin Induces Apoptosis in Human Prostate Carcinoma PC-3 Cells through G2/M Phase Arrest
Vitexicarpin Induces Apoptosis in Human Prostate Carcinoma PC-3 Cells through G2/M Phase Arrest
复制标题
牡荆素通过 G2/M 期阻滞诱导人前列腺癌 PC-3 细胞凋亡
DOI：
10.7314/apjcp.2012.13.12.6369
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Yang, Hong
中科院分区：
文献类型：
--
作者：
Meng, Fan-Min;Yang, Jing-Bo;Yang, Hong
牡荆素（3 '，5-二羟基-3，4'，6，7-四甲氧基黄酮），从蔓荆子（Vitex rotundifolia Linne fil.）中分离的多甲氧基黄酮，长期以来一直被用作传统中药中的抗炎草药。据报道，牡荆素可以抑制各种癌细胞的生长。然而，还没有报道阐明其对人前列腺癌细胞的作用。本研究旨在探讨牡荆素对PC-3细胞的凋亡诱导作用及其分子机制。MTT实验表明，牡荆素剂量依赖性地抑制PC-3细胞的生长，IC_（50）近似于28.8 μ M。Hoechst 33258染色进一步揭示了牡荆素诱导的凋亡性细胞死亡。采用PI/Annexin V-FITC双染和流式细胞术检测牡荆素对PC-3细胞凋亡的影响。结果表明，牡荆素诱导PC-3细胞凋亡的同时，细胞周期阻滞在G2/M期。此外，我们的研究表明，牡荆素诱导PC-3细胞凋亡与上调促凋亡蛋白Bax，下调抗凋亡蛋白Bcl-2，细胞色素c从线粒体释放和线粒体膜电位降低。提示牡荆素有可能成为前列腺癌治疗的先导药物。
Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an IC50 similar to 28.8 mu M. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.