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Ormeloxifene efficiently inhibits ovarian cancer growth.

Abstract
Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer.
AuthorsDiane M Maher, Sheema Khan, Jordan L Nordquist, Mara C Ebeling, Nichole A Bauer, Lucas Kopel, Man Mohan Singh, Fathi Halaweish, Maria C Bell, Meena Jaggi, Subhash C Chauhan
JournalCancer letters (Cancer Lett) Vol. 356 Issue 2 Pt B Pg. 606-12 (Jan 28 2015) ISSN: 1872-7980 [Electronic] Ireland
PMID25306892 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Benzopyrans
  • ormeloxifene
Topics
  • Animals
  • Apoptosis (drug effects)
  • Benzopyrans (pharmacology)
  • Blotting, Western
  • Cell Cycle (drug effects)
  • Cell Proliferation (drug effects)
  • Female
  • Flow Cytometry
  • Humans
  • Membrane Potential, Mitochondrial (drug effects)
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms (drug therapy, metabolism, pathology)
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

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