Effects of alpha-lipoic acid on redox status, cell proliferation and migration in PC-3 and DU-145 human prostate cancer cells

• Main Authors: Wen-Chun Shin, 施汶均
• Other Authors: 張菡馨
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/03438352692233709430

碩士 === 中山醫學大學 === 營養學研究所 === 101 === We examined the effects of α-lipoic acid (ALA) on cell behaviors in human prostate cancer cell lines with metastatic characteristic, PC-3 and DU-145. Cells were treated with concentrations of α-lipoic acid (0, 50, 100, 500, 750, 1000 μM) for studying the growth of prostate cancer cells by trypan blue assay and its migration by wound healing test and the underlying mechanisms evaluated by matrix metalloproteinase (MMPs) activity. The results show that the growth of PC-3 cell increases following the treatment of moderate concentrations (50, 100μM) of α-lipoic acid after 72 hour, while high concentration of ALA (500μM) significantly inhibited the proliferation (p＜0.05). Differential pattern of proliferation was observed in DU-145 cell, in which increasing concentrations significantly inhibited cell growth after 72 hours treatment (p＜0.05). ALA promoted distance of migration of PC-3 cells along with the increasing concentrations. While in DU-145 cells, migration distance was promoted only in the low concentrations (50, 100μM), but inhibited in the higher concentration (500, 750, 1000μM). Zymographic analysis of matrix metalloproteinase (MMPs) activity showed that, ALA treatment significantly increased the MMP-2 and MMP-9 activity in PC-3 cell after 72 hours (p＜0.01). In DU-145, the MMP-2 and MMP-9 activity significantly increased in low concentration of α-lipoic acid (50μM) for 72 hours (p＜0.01), but slightly reduced in 750, 1000μM groups. Test of a series of intracellular antioxidant indices, including GSH, GSSG, GPx, GR, GST, SOD, CAT, found that α-lipoic acid treatment may alter intracellular redox balance as the followings: intracellular glutathione (GSH) concentration and the GSH / GSSG ratio tended to increase, which may indirectly linked to either subsequent cell proliferation or apoptosis. Western blot analysis of apoptosis-related proteins revealed that proteins Caspase 3, and Caspase 9 increased by α-lipoic acid, and subsequently promote apoptosis. Our results indicate that, α-lipoic acid may enhance human prostate cancer cell apoptpsis but simultaneously promote metastasis through the alteration of GSH redox ratio, and caspase 3, caspase 9 protein expression.