Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells
Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells
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DOI：
10.1002/ijc.23485
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发表时间：
2008-07-01
影响因子：
6.4
通讯作者：
Agarwal, Rajesh
中科院分区：
文献类型：
--
作者：
Deep, Gagan;Oberlies, Nicholas H.;Agarwal, Rajesh
前列腺癌（PCa）是男性癌症相关死亡的主要原因;有必要采取紧急措施来降低这种致命的恶性肿瘤。水飞蓟素是一种已知的癌症化学预防剂，但其成分的相对抗癌功效仍不清楚。在此，我们比较了从水飞蓟素中分离的7种纯黄酮木脂体化合物，即水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A、异水飞蓟宾B、水飞蓟宁、异水飞蓟宁、水飞蓟素和异水飞蓟素在晚期人前列腺癌PC 3细胞中的功效。水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A、异水飞蓟宾B、水飞蓟宾和水飞蓟素强烈抑制PC 3细胞的殖民地形成（p < 0.001），而水飞蓟素、水飞蓟素和异水飞蓟素则有轻微的抑制作用（p < 0.05）。使用细胞生长和死亡测定，我们确定异水飞蓟宾B作为最有效的异构体。细胞周期的FACS分析还显示，在处理72小时后，水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A、异水飞蓟宾B、水飞蓟宾和水飞蓟素处理导致PC 3细胞中强烈的细胞周期停滞，而水飞蓟宁、水飞蓟素和异水飞蓟素的作用是边缘的（如果有的话）。Western印迹分析还显示这些化合物对细胞周期调节剂-细胞周期蛋白（D、E、A和B）、CDK（Cdk 2、4和Cdc 2）、CDK 1（p21.和p27）和其它细胞周期调节剂（Skp 2、Cdc 25 A、B、C和Chk 2）。这项研究为每种水飞蓟素成分之间的差异抗癌潜力提供了进一步的证据，这将对设计更好的水飞蓟素制剂对抗前列腺癌和其他癌症具有潜在的影响。(C)2008 Wiley-Liss，Inc.
Prostate cancer (PCa) is the leading cause of cancer-related deaths in men; urgent measures are warranted to lower this deadly malignancy. Silymarin is a known cancer chemopreventive agent, but the relative anticancer efficacy of its constituents is still unknown. Here, we compared the efficacy of 7 pure flavonolignan compounds isolated from silymarin, namely silybin A, silybin B, isosilybin A, isosilybin B, silydianin, isosilydianin, silychristin and isosilychristin, in advanced human PCa PC3 cells. Silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin strongly inhibited the colony formation by PC3 cells (p < 0.001), while silydianin, silychristin and isosilychristin had marginal effect (p < 0.05). Using cell growth and death assays, we identified isosilybin B as the most effective isomer. FACS analysis for cell cycle also showed that silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin treatment resulted in strong cell cycle arrest in PC3 cells after 72 hr of treatment, while the effect of silydianin, silychristin and isosilychristin was marginal (if any). Western blot analysis also showed the differential effect of these compounds on the levels of cell cycle regulators-cyclins (D, E, A and B), CDKs (Cdk2, 4 and Cdc2), CDKIs (p21. and p27) and other cell cycle regulators (Skp2, Cdc25A, B, C and Chk2). This study provided further evidence for differential anticancer potential among each silymarin constituent, which would have potential implications in devising better formulations of silymarin against prostate and other cancers. (C) 2008 Wiley-Liss, Inc.