Lasalocid induces cytotoxic apoptosis and cytoprotective autophagy through reactive oxygen species in human prostate cancer PC-3 cells

Kwang Youn Kim, Sang Hun Kim, Sun Nyoung Yu, Sul Gi Park, Young Wook Kim, Hyo Won Nam, Hyun Hee An, Hak Sun Yu, Young Woo Kim, Jae Hoon Ji, Young Kyo Seo, Soon Cheol Ahn

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Lasalocid is an antibiotic from the group of carboxylic ionophores, produced by Streptomyces lasaliensis. But there was limited information of lasalocid on human prostate cancer cells. In the present studies, to better understand its effect in human prostate cancer cells, apoptosis and autophagy associated with possible signal pathways in vitro was examined. Our study showed that lasalocid mediated cell cycle arrest in G0/G1 phase by reducing G1 phase dependent proteins, indicating entering into apoptotic cell death pathway. Lasalocid-induced apoptosis was involved with reactive oxygen species (ROS) production, and mitochondrial hyperpolarization. In addition, lasalocid induced autophagy through microtubule-associated protein 1 light chain 3 (LC-3)-II conversion, acidic vesicular organelles formation and GFP-LC-3 punctuate, which was inhibited by 3-methyladenine (3-MA), a widely used pharmacological inhibitor of autophagy. Furthermore, the autophagic phenomena were mediated by production of ROS, confirming that inhibition of ROS with N-acetyl-L-cysteine, a ROS inhibitor, attenuated lasalocid-triggered autophagy. Inhibition of autophagy with 3-MA enhanced the lasalocid-induced apoptosis through enhanced ROS generation. Taken together, lasalocid should be useful in the search for new potential chemotherapeutic agents for understanding the molecular mechanisms of anticancer in prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)1016-1024
Number of pages9
JournalBiomedicine and Pharmacotherapy
Volume88
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Cell cycle arrest
  • Lasalocid
  • Prostate cancer
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology

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