Suppression of autophagy exacerbates Mefloquine-mediated cell death

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• 作者：Ji Hyun Shin ; So Jung Park ; Yoon Kyung Jo ; Eun Sung Kim ; Hee Kang ; Ji-Ho Park ; Eunjoo H. Lee ; Dong-Hyung Cho ; ^{dhcho@khu.ac.kr}
• 关键词：Mefloquine ; Autophagy ; Cytotoxicity ; SH-SY5Y cell ; ATG
• 刊名：Neuroscience Letters
• 出版年：2012
• 出版时间：2 May, 2012
• 年：2012
• 卷：515
• 期：2
• 页码：162-167
• 全文大小：752 K

文摘

Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6. The autophagy was also completely blocked in ATG5 deficient mouse embryonic fibroblast cells. Moreover, suppression of autophagy significantly intensified Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma cells.