상위피인용논문
- 조회592
Kwang-Youn Kima, Sun-Nyoung Yua, Sun-Yi Leeb, Sung-Sik Chunc, Yong-Lark Choid, Yeong-Min Parka, Chung Seog Songe, Bandana Chatterjeee, Soon-Cheol Ahna,e,f,*
a Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea
b Citrus Research Station, National Institute of Horticultural & Herbal Science, RDA, Jeju 699-946, Republic of Korea
c Department of Food Science, International University of Korea, Jinju 660-759, Republic of Korea
d Department of Biotechnology, Faculty of Natural Resources and Life Science Dong-A University, Busan 604-714, Republic of Korea
e Department of Molecular Medicine & Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
f Medical Research Institute, Pusan National University, Yangsan 626-870, Republic of Korea
*Corresponding author : Soon-Cheol Ahn
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.
Keywords : Salinomycin; Prostate cancer; Apoptosis; PC-3 cells; Reactive oxygen species; Mitochondrial membrane potential; N-Acetylcysteine
논문정보
- Research article
- 2011년 09월 (BRIC 등록일 2019-04-08)
- 국내(교신)+국외 연구진
- 120회 이상 인용된 논문
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