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

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

  • Biomed Pharmacother. 2017 Apr:88:1016-1024. doi: 10.1016/j.biopha.2017.01.140.
Kwang-Youn Kim 1,  Sang-Hun Kim 2,  Sun-Nyoung Yu 2,  Sul-Gi Park 2,  Young-Wook Kim 2,  Hyo-Won Nam 2,  Hyun-Hee An 2,  Hak-Sun Yu 3,  Young Woo Kim 1,  Jae-Hoon Ji 4,  Young-Kyo Seo 5,  Soon-Cheol Ahn 6
Affiliations

Affiliations

  • 1 Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
  • 2 Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
  • 3 Department of Parasitology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University, Yangsan 50612, Republic of Korea.
  • 4 Genome Instability Research Center, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
  • 5 School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • 6 Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: ahnsc@pusan.ac.kr.
PMID: 28178613 DOI: 10.1016/j.biopha.2017.01.140
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.

Keywords

Apoptosis; Autophagy; Cell cycle arrest; Lasalocid; Prostate cancer; Reactive oxygen species.

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