Salinomycin Induces Apoptosis via Death Receptor-5 up-regulation in Cisplatin-resistant Ovarian Cancer Cells

Authors
BIDUR PARAJULISO-JIN SHINSANG-HOON KWONSOON-DO CHAROSA CHUNGWON-JIN PARKHYUN-GYO LEECHI-HEUM CHO
Department
Dept. of Obstetrics & Gynecology (산부인과학); Institute for Cancer Research (암연구소)
Issue Date
2013
Citation
Anticancer Research, Vol.33(4) : 1457-1462, 2013
ISSN
0250-7005
Abstract
Background: Chemo-resistance to cisplatin-centered cancer therapy is a major obstacle to effective disease treatment. Recently, salinomycin was proven to be highly-effective for the elimination of cancer stem cells both in vitro and in vivo. The objective of the present study was to evaluate the anticancer properties of salinomycin in cisplatin-resistant ovarian cancer cells (A2780cis). Materials and Methods: The tetrazolium dye (MTT) assay was used to determine cell viability. Flow cytometric analysis was performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis-related proteins was evaluated by western blot analysis. Results: Cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. Flow cytometry showed an increase in sub-G1 phase cells. Salinomycin increased the expression of death receptor-5 (DR5), caspase-8 and Fas-associated protein with death domain (FADD). A decline in the expression of FLICE-like inhibitory protein (FLIP), activation of caspase-3 and increased poly ADP-ribose polymerase (PARP) cleavage, triggered apoptosis. Furthermore, annexin-V staining also revealed the apoptotic induction. Conclusion: These findings provide important insights regarding the activation of caspase-8 and DR5, to our knowledge, for the first time in salinomycin-treated cisplatin-resistant ovarian cancer and demonstrate that salinomycin could be a prominent anticancer agent.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35061
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Institute for Cancer Research (암연구소)
Keimyung Author(s)
신소진; 권상훈; 차순도; 조치흠
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