天然化合物维康醇选择性诱导前列腺癌细胞凋亡的研究

Nature compound alternol preferentially induce apoptosis in prostate cancer cells

目的观察新型天然化合物维康醇对于恶性前列腺细胞的抗肿瘤作用，并初步探讨其药物作用机制。方法通过western blot检测维康醇在不同前列腺癌细胞株及正常前列腺上皮诱导凋亡的作用，通过流式细胞技术方式分析前列腺癌细胞凋亡的具体类型及凋亡率变化，在相同药物浓度下与传统化疗药物疗效进行对比。结果通过对凋亡标志物的半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3及聚腺苷二磷酸核糖聚合酶（PARP）的检测确认了维康醇诱导的细胞死亡方式为凋亡。通过进一步流式细胞计数分析维康醇诱导的前列腺癌细胞凋亡方式主要是晚期凋亡，12h其诱导Pc3晚期细胞凋亡率[（14．8±1．2）％]较正常前列腺细胞株BPH1[（6．8±1．1）％]及前列腺癌细胞株DU145[（3．9±0．8）％]明显增高，最后通过与传统化疗药物伊立替康（CPT-11）、多西他赛及紫杉醇进行对比，western blot结果显示相同浓度下维康醇诱导前列腺癌细胞凋亡的效果更为显著。结论维康醇可选择性杀伤除DU145细胞以外的全部前列腺癌细胞而对正常前列腺上皮细胞无明显影响，维康醇诱导的这种细胞死亡方式主要是时间依赖性的晚期凋亡，且与传统的化疗药物比较，其抗肿瘤效果更佳。

Objective In this study, we evaluated the anti-cancer effect of a newly isolated natural compound Alternol in prostate cancer cells. The pharmacological mechanism was discussed preliminarily. Methods Utilizing western blotting, the indicators of apoptosis-cysteinyl aspartate-specific protease （Caspase）-3 and poly adenosine diphosphate-ribose polymerase （PARP）-were tested after Alternol incubation with different prostate cancer cell lines and normal prostatic epithelial cell lines. And then we used flow cytometer to clear the apoptosis type and apoptosis rate. Finally, we compared the anti-cancer effect between Ahernol and other and traditional chemotherapy drugs in the same drug concentration. Results Western blotting revealed that Ahernol-induced cell death was an apoptotic response as evidenced by the appearance of apoptosis hallmarks such as Caspase-3 processing and PARP cleavage. Flow cytometer analyses showed Alternol induced prostate cancer cell death was a late apoptosis manner, at 12 h the PC3 group late apoptosis rate increased significantly [ （14.8±1.2）% ] compared with BPH1 [ （6.8±1.1 ） % ] and DU145 group [ （3.9±0.8） % ]. Finally, we compared the anti-cancer effect between Alternol and traditional chemotherapy drugs such as CPT-11, Docetaxel and Paclitaxel. Western blotting showed that Ahernol could induce more prostate cancer cell apoptosis in the same drug concentration than and traditional chemotherapy drugs. Conclusion Ahernol was capable of inducing intracellular apoptotic cell death preferentially in prostate cancer cells except DU145 cell lines and normal prostate epithelial cell lines. The apoptotic cell death was a time dependent late apoptosis. Compared with traditional chemotherapy drugs, Ahernol had a better anti-cancer effect.