title: Effects of salinomycin on human ovarian cancer cell line OV2008 are associated with modulating p38 MAPK.
abstract: This study investigated the anticancer effect and mechanism of salinomycin, a selective inhibitor of cancer stem cell, on human ovarian cancer cell line OV2008 in vitro and in vivo. The growth inhibitory effect of salinomycin on ovarian cancer cell line OV2008 was determined by measuring cell viability using the resazurin reduction assay. Apoptotic nuclear morphology was visualized by 4,6-diamino-2-phenylindole staining technique. The percentages of apoptotic cells and cell cycle parameters were detected by flow cytometry. The activity of p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Bio-Plex phosphoprotein assay. In vivo activity of salinomycin was assayed through tumor growth. Salinomycin caused concentration- (0.01-200 μM) and time-dependent (24-72 h) growth inhibitory effects in OV2008. Cell nuclear morphology observations showed that salinomycin-treated OV2008 cells displayed typical apoptotic characteristics. Salinomycin significantly increased the percentages of apoptotic cells in OV2008, showing a concentration- and time-dependent manner. There was no cell cycle arrest in the G1/G0, S, and G2/M phases between salinomycin-treated cells and control cells. Salinomycin also enhanced the phosphorylation of p38 MAPK. Moreover, salinomycin significantly inhibited the growth of the ovarian xenograft tumors. Salinomycin exhibited significant growth inhibition and induction of apoptosis in the human ovarian cancer cell line OV2008. The data suggested that salinomycin-induced apoptosis in OV2008 might be associated with activating p38 MAPK and merits further investigations.
authors: Laboratory for Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, Hebelstrasse 20, 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: Johannes
authors: J
authors: Bitzer
authors: Xiao Yan
authors: XY
authors: Zhong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000095662:Polyether Polyketides
chemical_list: D000900:Anti-Bacterial Agents; D011714:Pyrans; D048051:p38 Mitogen-Activated Protein Kinases; C010327:salinomycin; D000095662:Polyether Polyketides