Tian Xue, Song Hae Seong, Cho Young Mi, Park Bongkyun, Song Yoon-Jae, Jang Sunphil, Kang Se Chan
Department of Life Science, Gachon University, Seongnam-si Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin-si, Korea.
Medicine (Baltimore). 2017 Jul;96(30):e7606. doi: 10.1097/MD.0000000000007606.
To demonstrate the mechanisms of the curative effect of Saussurea lappa ethanol extract (SLE) against prostate cancer, we evaluated the effect of SLE on the induction of apoptosis and autophagy and investigated whether SLE-induced autophagy exerts a pro-survival or pro-apoptotic effect in lymph node carcinoma of the prostate (LNCaP) prostate cancer cells. SLE was prepared using 100% ethanol and added to LNCaP cells for 24 hours. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell apoptosis was evaluated by Tali assay. The expression of apoptosis-related mRNA and proteins was analyzed by quantitative real-time RT-PCR and western blotting. SLE treatment decreased the viability of LNCaP cells and increased Bax expression while suppressing the expression of pro-caspases-8/9/3, PARP, Bid, and Bcl-2, thereby inducing apoptosis in LNCaP cells. Cell proliferation related proteins, including p-Akt, androgen receptor, and prostate-specific antigen, were suppressed by SLE treatment. SLE also induced autophagy in LNCaP cells, and inhibition of autophagy enhanced the apoptosis induced by SLE treatment. These results suggest that SLE exerts anticancer effects through the induction of both cellular apoptosis and autophagy, and apoptotic cell death can be facilitated by blocking autophagy in SLE-treated LNCaP cells. Therefore, SLE might be a potential anticancer agent for the treatment of prostate cancer.
为了阐明木香乙醇提取物（SLE）对前列腺癌的治疗作用机制，我们评估了SLE对细胞凋亡和自噬诱导的影响，并研究了SLE诱导的自噬在前列腺淋巴结癌（LNCaP）前列腺癌细胞中发挥的是促生存还是促凋亡作用。使用100%乙醇制备SLE，并将其添加到LNCaP细胞中作用24小时。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐法测定细胞活力，并通过Tali法评估细胞凋亡。通过定量实时RT-PCR和蛋白质印迹分析凋亡相关mRNA和蛋白质的表达。SLE处理降低了LNCaP细胞的活力，增加了Bax表达，同时抑制了前半胱天冬酶-8/9/3、PARP、Bid和Bcl-2的表达，从而诱导LNCaP细胞凋亡。SLE处理抑制了包括p-Akt、雄激素受体和前列腺特异性抗原在内的细胞增殖相关蛋白。SLE还诱导LNCaP细胞自噬，抑制自噬增强了SLE处理诱导的凋亡。这些结果表明，SLE通过诱导细胞凋亡和自噬发挥抗癌作用，并且在SLE处理的LNCaP细胞中阻断自噬可促进凋亡细胞死亡。因此，SLE可能是一种治疗前列腺癌的潜在抗癌药物。
