title: Antitumor properties of salinomycin on cisplatin-resistant human ovarian             cancer cells in vitro and in vivo: involvement of p38 MAPK activation.
abstract: In order to search for alternative agents to overcome chemoresistance during the treatment of ovarian cancer, this study aimed to examine the anticancer effects and action mechanism of salinomycin, a selective inhibitor of cancer stem cells, on cisplatin-resistant human ovarian cancer cell lines in vitro and in vivo. The concentration- (0.01-200 µM) and time‑dependent (24-72 h) growth inhibitory effects of salinomycin were observed in the ovarian cancer cell lines OV2008, C13, A2780, A2780-cp, SKOV3 and OVCAR3, by measuring cell viability using the resazurin reduction assay. The IC50 (24 h) range of salinomycin on the six cell lines was found to be 1.7-7.4 µM. After cisplatin-resistant C13 cells were treated with salinomycin, the percentage of apoptotic cells determined by flow cytometry was significantly increased, in a concentration- and time‑dependent manner. However, no cell cycle arrest was detected in the G1/G0, S and G2/M phases in the salinomycin‑treated and control cells. The Bio-Plex phosphoprotein 5-plex assay (Akt, IκB-α, ERK1/2, JNK and p38 MAPK) demonstrated a marked time- and concentration‑dependent increase in the phosphorylation of p38 MAPK, subsequent to salinomycin treatment. Moreover, salinomycin significantly suppressed tumor growth in a tumor xenograft model. These findings suggested that salinomycin efficiently inhibits the cisplatin-resistant human ovarian cancer cell line growth through the induction of apoptosis, potentially associated with the p38 MAPK activation.
authors: Laboratory for Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, CH-4031 Basel, Switzerland.
authors: Bei
authors: B
authors: Zhang
authors: Xueya
authors: X
authors: Wang
authors: Fengfeng
authors: F
authors: Cai
authors: Weijie
authors: W
authors: Chen
authors: Uli
authors: U
authors: Loesch
authors: Xiao Yan
authors: XY
authors: Zhong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011714:Pyrans / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000095662:Polyether Polyketides
chemical_list: D002945:Cisplatin; D051057:Proto-Oncogene Proteins c-akt; D011714:Pyrans; D048051:p38 Mitogen-Activated Protein Kinases; C010327:salinomycin; D000095662:Polyether Polyketides