Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization

Kwang Youn Kim, Sun Nyoung Yu, Sun Yi Lee, Sung Sik Chun, Yong Lark Choi, Yeong Min Park, Chung Seog Song, Bandana Chatterjee, Soon Cheol Ahn

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

The anticancer activity of salinomycin has evoked excitement due to its recent identification as a selective inhibitor of breast cancer stem cells (CSCs) and its ability to reduce tumor growth and metastasis in vivo. In prostate cancer, similar to other cancer types, CSCs and/or progenitor cancer cells are believed to drive tumor recurrence and tumor growth. Thus salinomycin can potentially interfere with the end-stage progression of hormone-indifferent and chemotherapy-resistant prostate cancer. Androgen-responsive (LNCaP) and androgen-refractive (PC-3, DU-145) human prostate cancer cells showed dose- and time-dependent reduced viability upon salinomycin treatment; non-malignant RWPE-1 prostate cells were relatively less sensitive to drug-induced lethality. Salinomycin triggered apoptosis of PC-3 cells by elevating the intracellular ROS level, which was accompanied by decreased mitochondrial membrane potential, translocation of Bax protein to mitochondria, cytochrome c release to the cytoplasm, activation of the caspase-3 and cleavage of PARP-1, a caspase-3 substrate. Expression of the survival protein Bcl-2 declined. Pretreatment of PC-3 cells with the antioxidant N-acetylcysteine prevented escalation of oxidative stress, dissipation of the membrane polarity of mitochondria and changes in downstream molecular events. These results are the first to link elevated oxidative stress and mitochondrial membrane depolarization to salinomycin-mediated apoptosis of prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)80-86
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume413
Issue number1
DOIs
StatePublished - Sep 16 2011

    Fingerprint

Keywords

  • Apoptosis
  • Mitochondrial membrane potential
  • N-Acetylcysteine
  • PC-3 cells
  • Prostate cancer
  • Reactive oxygen species
  • Salinomycin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this