南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (6): 953-959.doi: 10.12122/j.issn.1673-4254.2021.06.21

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褐藻素通过线粒体通路和氧化应激诱导前列腺癌细胞凋亡

李国平,常秀亭,罗小菊,赵映淑,王为服,康新立   

  • 出版日期:2021-06-20 发布日期:2021-07-05

Fucoxanthin induces prostate cancer PC-3 cell apoptosis by causing mitochondria dysfunction and oxidative stress

  • Online:2021-06-20 Published:2021-07-05

摘要: 目的 旨在探讨褐藻素(Fx)对人前列腺癌PC-3细胞凋亡的影响及其作用机制。方法 采用相应的试剂盒检测PC-3细胞活力和细胞凋亡。荧光探针染色检测PC-3细胞中的线粒体膜电位、线粒体形态和线粒体超氧化物。同时采用相应的试剂盒检测PC-3细胞中三磷酸腺苷、过氧化氢、丙二醛和超氧化物的含量以及总抗氧化能力。Western blot方法检测PC-3细胞中Bcl-2、Bax和细胞色素c蛋白的表达。采用相应的试剂盒检测PC-3细胞中caspase-9和caspase-3/7活性。结果 Fx呈时间和剂量依赖性地抑制PC-3细胞活力,呈剂量依赖性地诱导PC-3细胞凋亡(P<0.05)。经Fx处理后,PC-3细胞中的线粒体膜电位水平降低,线粒体碎片化,线粒体超氧化物水平升高(P<0.05),且Fx的作用效果成剂量依赖性。Fx剂量依赖性地降低PC-3细胞中的三磷酸腺苷水平和总抗氧化能力,剂量依赖性地增加过氧化氢、丙二醛和超氧化物的含量(P<0.05)。经Fx处理后,PC-3细胞中Bax和细胞质中细胞色素c的水平呈剂量依赖性增加,PC-3细胞中Bcl-2和线粒体中细胞色素c的水平呈剂量依赖性降低(P<0.05)。结论 Fx通过引发线粒体功能障碍导致氧化应激和激活线粒体介导的凋亡信号通路诱导PC-3细胞凋亡,提示Fx有望成为治疗前列腺癌的潜在药物。

关键词: 褐藻素;前列腺癌;细胞凋亡;线粒体;氧化应激

Abstract: Objective To investigate the apoptosis-inducing effect of fucoxanthin in human prostate cancer PC-3 cells and the underlying mechanism. Methods The viability and apoptosis of PC-3 cells treated with fucoxanthin were analyzed using commercial kits, and the mitochondrial membrane potential, mitochondrial morphology and mitochondrial superoxide were detected using fluorescence probe staining. The contents of ATP, H2O2, malondialdehyde (MDA), superoxide and the total antioxidant capacity of PC-3 cells were determined. The protein expressions of Bcl-2, Bax and cytochrome c were detected with Western blotting, and the activity of caspase-9 and caspase-3/7 was detected using corresponding kits. Results Fucoxanthin significantly inhibited the viability of PC-3 cells in a time- and dose-dependent manner, and dose-dependently induced apoptosis of the cells (P<0.05). Fucoxanthin-treated PC-3 cells showed significantly decreased mitochondrial membrane potential, mitochondrial fragmentation and increased superoxide level in the mitochondria (P<0.05), and these effects of fucoxanthin were dose- dependent. Fucoxanthin dose-dependently decreased ATP level and the total antioxidant capacity of PC-3 cells, increased the contents of H2O2, MDA and superoxide (all P<0.05), enhanced the protein expressions of Bax and cytochrome c in the cytoplasm, and lowered the protein expressions of Bcl-2 and cytochromes in the mitochondria (P<0.05). Conclusions Fucoxanthin induces apoptosis of PC-3 cells by triggering mitochondrial dysfunction to cause oxidative stress and by activating mitochondria-mediated apoptotic signaling pathways, suggesting its potential in prostate cancer treatment.

Key words: fucoxanthin; prostate cancer; apoptosis; mitochondria; oxidative stress