title: Suppression of autophagy exacerbates Mefloquine-mediated cell death.
abstract: 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.
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-Do, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jo
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Kim
authors.forename: Hee
authors.initials: H
authors.lastname: Kang
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Eunjoo H
authors.initials: EH
authors.lastname: Lee
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D015767:Mefloquine / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects*
chemical_list: D015767:Mefloquine