Barve Avantika, Khor Tin Oo, Hao Xingpei, Keum Young-Sam, Yang Chung S, Reddy Bandaru, Kong Ah-Ng Tony
Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Pharm Res. 2008 Sep;25(9):2181-9. doi: 10.1007/s11095-008-9574-7. Epub 2008 Apr 25.
Prior studies from our laboratory have demonstrated the efficacy of a combined treatment of low doses of dietary agents curcumin and phenylethylisothiocyanate in effectively suppressing prostate cancer in vitro in human prostate cancer PC3 cells as well as in vivo in immunodeficient mice implanted with PC3 cells. Hence, this study was undertaken to examine the potential chemopreventive properties of the two agents against transgenic adenocarcinoma of the mouse prostate.
The efficacy of AIN-76A diet supplemented with 2% curcumin or 0.05% PEITC or a combination of 1% curcumin and 0.025% PEITC for periods of 10 and 16 weeks was tested against adenocarcinoma of the mouse prostate. Immunohistochemistry and Western blot analysis were used to examine the expression of proliferation and apoptotic biomarkers. All statistical tests were two-sided.
Supplementing AIN-76A diet with dietary phytochemicals curcumin or PEITC either alone or in combination, significantly decreased incidence of prostate tumor formation (P = 0.0064). Immunohistochemistry revealed a significant inhibition of high-grade PIN (P = 0.0006, 0.000069, 0.00029 for a treatment period of 10 weeks and P = 0.02582, 0.022179, 0.0317 for a treatment period of 16 weeks) along with decreased proliferation and increased apoptotic index in the curcumin, PEITC or curcumin and PEITC treated animals, respectively. Furthermore, Western blot analysis revealed that downregulation of the Akt signaling pathway may in part play a role in decreasing cell proliferation ultimately retarding prostate tumor formation.
Our data lucidly evidence the chemopreventive merits of dietary phytochemicals curcumin and PEITC in suppressing prostate adenocarcinoma.
我们实验室之前的研究已证明，低剂量饮食剂姜黄素和苯乙基异硫氰酸酯联合治疗在体外对人前列腺癌PC3细胞以及在体内对植入PC3细胞的免疫缺陷小鼠有效抑制前列腺癌。因此，本研究旨在检测这两种药物对小鼠前列腺转基因腺癌的潜在化学预防特性。
测试了补充2%姜黄素或0.05%苯乙基异硫氰酸酯或1%姜黄素与0.025%苯乙基异硫氰酸酯组合的AIN-76A饮食在10周和16周期间对小鼠前列腺腺癌的疗效。采用免疫组织化学和蛋白质印迹分析来检测增殖和凋亡生物标志物的表达。所有统计检验均为双侧检验。
在AIN-76A饮食中单独或联合添加饮食植物化学物质姜黄素或苯乙基异硫氰酸酯，显著降低了前列腺肿瘤形成的发生率（P = 0.0064）。免疫组织化学显示，在姜黄素、苯乙基异硫氰酸酯或姜黄素与苯乙基异硫氰酸酯处理的动物中，高级别前列腺上皮内瘤变受到显著抑制（治疗10周时P = 0.0006、0.000069、0.00029，治疗16周时P = 0.02582、0.022179、0.0317），同时增殖减少，凋亡指数增加。此外，蛋白质印迹分析显示，Akt信号通路的下调可能在一定程度上参与减少细胞增殖，最终延缓前列腺肿瘤形成。
我们的数据清楚地证明了饮食植物化学物质姜黄素和苯乙基异硫氰酸酯在抑制前列腺腺癌方面的化学预防优点。
