title: 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.
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maher
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Sheema
authors.initials: S
authors.lastname: Khan
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Nordquist
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Mara C
authors.initials: MC
authors.lastname: Ebeling
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Bauer
authors.affiliation: Department of Chemistry & Biochemistry, South Dakota State University, SD 57007, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Kopel
authors.affiliation: Saraswati Dental College, Lucknow, Uttar Pradesh, India.
authors.forename: Man Mohan
authors.initials: MM
authors.lastname: Singh
authors.affiliation: Department of Chemistry & Biochemistry, South Dakota State University, SD 57007, USA.
authors.forename: Fathi
authors.initials: F
authors.lastname: Halaweish
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA; Departments of OB/GYN and Basic Biomedical Science Division, Sanford School of Medicine, The University of South Dakota, SD 57105, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bell
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: schauha1@uthsc.edu.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D001578:Benzopyrans; C508548:ormeloxifene
keywords: Apoptosis; Cisplatin resistance; Novel therapies; Ormeloxifene; Ovarian cancer; Xenograft mice