Lasalocid induces cytotoxic apoptosis and cytoprotective autophagy through reactive oxygen species in human prostate cancer PC-3 cells.
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/G1phase by reducing G1phase 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.
Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Kwang-Youn
KY
Kim
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Sang-Hun
SH
Kim
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Sun-Nyoung
SN
Yu
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Sul-Gi
SG
Park
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Young-Wook
YW
Kim
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Hyo-Won
HW
Nam
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Hyun-Hee
HH
An
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.
Hak-Sun
HS
Yu
Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Young Woo
YW
Kim
Genome Instability Research Center, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Jae-Hoon
JH
Ji
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
Young-Kyo
YK
Seo
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.
Soon-Cheol
SC
Ahn
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007832:Lasalocid / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D007832:Lasalocid
Apoptosis; Autophagy; Cell cycle arrest; Lasalocid; Prostate cancer; Reactive oxygen species