Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling

Kun Huang Yan, Chih Jung Yao, Chi Hao Hsiao, Ke Hsun Lin, Yung Wei Lin, Yu-Ching Wen, Chung Chi Liu, Ming De Yan, Shuang En Chuang, Gi Ming Lai, Liang Ming Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mefloquine (MQ) is a prophylactic anti-malarial drug. Previous studies have shown that MQ induces oxidative stress in 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.

Original languageEnglish
Pages (from-to)1541-1545
Number of pages5
JournalOncology Letters
Volume5
Issue number5
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Mefloquine
Extracellular Signal-Regulated MAP Kinases
Adenosine Monophosphate
Protein Kinases
Reactive Oxygen Species
Prostatic Neoplasms
Phosphotransferases
lissamine rhodamine B
JNK Mitogen-Activated Protein Kinases
Mitochondrial Membrane Potential
Antimalarials
Growth
Cysteine
Cell Survival
Oxidative Stress
Down-Regulation
Phosphorylation
Staining and Labeling

Keywords

  • Hyperpolarization
  • Mefloquine
  • Mitochondrial membrane potential
  • N-acetyl cysteine
  • Prostate cancer
  • Reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling. / Yan, Kun Huang; Yao, Chih Jung; Hsiao, Chi Hao; Lin, Ke Hsun; Lin, Yung Wei; Wen, Yu-Ching; Liu, Chung Chi; Yan, Ming De; Chuang, Shuang En; Lai, Gi Ming; Lee, Liang Ming.

In: Oncology Letters, Vol. 5, No. 5, 10.2013, p. 1541-1545.

Research output: Contribution to journalArticle

Yan, Kun Huang ; Yao, Chih Jung ; Hsiao, Chi Hao ; Lin, Ke Hsun ; Lin, Yung Wei ; Wen, Yu-Ching ; Liu, Chung Chi ; Yan, Ming De ; Chuang, Shuang En ; Lai, Gi Ming ; Lee, Liang Ming. / Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling. In: Oncology Letters. 2013 ; Vol. 5, No. 5. pp. 1541-1545.
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