title: Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A.
abstract: OBJECTIVE
  Withaferin A, a natural withanolide, has shown anti-cancer properties in various cancers including breast cancer, but its effects in ovarian cancer remain unexplored. Notch 1 and Notch3 are critically involved in ovarian cancer progression. We decided to examine the effects of Withaferin A in ovarian carcinoma cell lines and its molecular mechanism of action including its regulation of Notch.
  
  
  METHODS
  The effects of Withaferin A were examined in CaOV3 and SKOV3 ovarian carcinoma cell lines using MTS assay, clonogenic assay, annexin V/propidium iodide flow cytometry, and cell cycle analysis. Western analysis was conducted to examine the molecular mechanisms of action.
  
  
  RESULTS
  Withaferin A inhibited the growth and colony formation of CaOV3 and SKOV3 cells by inducing apoptosis and cell cycle arrest. These changes correlated with down-regulation of Notch1, Notch3, cdc25C, total and phosphorylated Akt, and bcl-2 proteins.
  
  
  CONCLUSIONS
  Withaferin A inhibits CaOV3 and SKOV3 ovarian carcinoma cell growth, at least in part by targeting Notch1 and Notch3.
authors.affiliation: Department of Surgery, University of Kansas School of Medicine, Kansas City, KS 66160, USA. xzhang2@kumc.edu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Abbas K
authors.initials: AK
authors.lastname: Samadi
authors.forename: Katherine F
authors.initials: KF
authors.lastname: Roby
authors.forename: Barbara
authors.initials: B
authors.lastname: Timmermann
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cohen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D048708:Cell Growth Processes / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism; D054358:Withanolides / Q000494:pharmacology*; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; C499374:NOTCH3 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D054358:Withanolides; D051058:Oncogene Protein v-akt; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; C009684:withaferin A