title: Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling.
abstract: Mefloquine (MQ) is a prophylactic anti-malarial drug. Previous studies have shown that MQ induces oxidative stressin vitro. Evidence indicates that reactive oxygen species (ROS) may be used as a therapeutic modality to kill cancer cells. This study investigated whether MQ also inhibits prostate cancer (PCa) cell growth. We used sulforhodamine B (SRB) staining to determine cell viability. MQ has a highly selective cytotoxicity that inhibits PCa cell growth. The antitumor effect was most significant when examined using a colony formation assay. MQ also induces hyperpolarization of the mitochondrial membrane potential (MMP), as well as ROS generation. The blockade of MQ-induced anticancer effects by N-acetyl cysteine (NAC) pre-treatment confirmed the role of ROS. This indicates that the MQ-induced anticancer effects are caused primarily by increased ROS generation. Moreover, we observed that MQ-mediated ROS simultaneously downregulated Akt phosphorylation and activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and adenosine monophosphate-activated protein kinase (AMPK) signaling in PC3 cells. These findings provide insights for further anticancer therapeutic options.
authors.affiliation: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei Medical University, Taipei 11696;
authors.forename: Kun-Huang
authors.initials: KH
authors.lastname: Yan
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Yao
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Hsiao
authors.forename: Ke-Hsun
authors.initials: KH
authors.lastname: Lin
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Lin
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Wen
authors.forename: Chung-Chi
authors.initials: CC
authors.lastname: Liu
authors.forename: Ming-DE
authors.initials: MD
authors.lastname: Yan
authors.forename: Shuang-En
authors.initials: SE
authors.lastname: Chuang
authors.forename: Gi-Ming
authors.initials: GM
authors.lastname: Lai
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Lee
keywords: N-acetyl cysteine; hyperpolarization; mefloquine; mitochondrial membrane potential; prostate cancer; reactive oxygen species