Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells

详细信息    查看全文

• 作者：Sang-Hun Kim^a ; ¹ ; Young-Jun Choi^b ; Kwang-Youn Kim^c ; ¹ ; Sun-Nyoung Yu^a ; Young-Kyo Seo^c ; Sung-Sik Chun^d ; Kyung-Tae Noh^e ; Jeung-Tak Suh^f ; Soon-Cheol Ahn^a ; ^{ahnsc@pusan.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Salinomycin ; Apoptosis ; Autophagy ; Reactive oxygen species ; U2OS cells
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2016
• 出版时间：29 April 2016
• 年：2016
• 卷：473
• 期：2
• 页码：607-613
• 全文大小：899 K

文摘

Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore. It was reported to anticancer activity on various cancer cell lines. In this study, salinomycin was examined on apoptosis and autophagy through generation of reactive oxygen species (ROS) in osteosarcoma U2OS cells. Apoptosis, autophagy, mitochondrial membrane potential (MMP) and ROS were analyzed using flow cytometry. Also, expressions of apoptosis- and autophagy-related proteins were determined by western blotting. As a result, salinomycin triggered apoptosis of U2OS cells, which was accompanied by change of MMP and cleavage of caspases-3 and poly (ADP-ribose) polymerase. And salinomycin increased the expression of autophagy-related protein and accumulation of acidic vesicular organelles (AVO). Salinomycin-induced ROS production promotes both apoptosis and autophagy, as evidenced by the result that treatment of N-acetyl-l-cysteine (NAC), a ROS scavenger, attenuated both apoptosis and autophagy. In addition, inhibition of autophagy by 3-methyladenine (3 MA) enhanced the salinoymcin-induced apoptosis. Taken together, these results suggested that salinomycin-induced autophagy, as a survival mechanism, might be a potential strategy through ROS regulation in cancer therapy.