title: Apoptosis of human ovarian cancer cells induced by Paris chinensis dioscin via a Ca(2+)-mediated mitochondrion pathway.
abstract: BACKGROUND
  Study of the mechanisms of apoptosis in tumor cells is an important field of tumor therapy and cancer molecular biology. Apoptosis triggered by activation of the mitochondrial-dependent caspase pathway represents the main programmed cell death mechanism. The mitochondrial-dependent apoptosis pathway is activated by various intracellular stresses that induce permeabilization of the mitochondrial membrane, leading to cytochrome C release. This study was to investigate the anti-tumor effects of Dioscin from traditional Chinese anti-snake venom medicine Paris chinensis (PCD) and correlated mechanisms regarding apoptosis in human ovarian cancer SKOV3 cells.
  
  
  METHODS
  Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was evaluated by flow cytometry and Laser Scanning Confocal Microscope (LSCM) using Annexin-V/PI staining. Intracellular calcium ions were detected using fluorescence microscopy. The expression of apoptosis-related proteins cytochrome C and caspase-3 was measured by immunohistochemical staining.
  
  
  RESULTS
  PCD had an anti-proliferation effect on human ovarian cancer SKOV3 cells in a dose- and time-dependent manner. After treatment with PCD, the apoptotic rate significantly increased, and accompanied with the increased levels of caspase-3 and cytochrome C protein in SKOV3 cells. Morphological changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining. Moreover, intracellular calcium accumulation occurred in PCD-treated cells.
  
  
  CONCLUSIONS
  The molecular determinants of inhibition of cell proliferation as well as apoptosis of PCD may be associated with the activation of Ca2+-related m itochondrion pathway in SKOV3 cells.
authors.affiliation: Department of Pathology and Pathophysiology, Taian Medical University, Taian, China. ytgd98@yahoo.cn
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Gao
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Jiao
authors.forename: Shu-Tong
authors.initials: ST
authors.lastname: Yao
authors.forename: Hui
authors.initials: H
authors.lastname: Sang
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Si
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D031446:Trillium / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; C019357:dioscin; D045304:Cytochromes c; D053148:Caspase 3; D004144:Diosgenin; D002118:Calcium