Ormeloxifene efficiently inhibits ovarian cancer growth

Diane 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 Chauhan

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)606-612
Number of pages7
JournalCancer Letters
Volume356
Issue number2
DOIs
StatePublished - Jan 1 2015

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Ovarian Neoplasms
Growth
Cisplatin
Non-Steroidal Estrogens
Therapeutics
Drug Repositioning
Phosphorylation
Selective Estrogen Receptor Modulators
Cell Line
Cyclin E
Cyclin D1
Patient Safety
ormeloxifene
Contraception
Heterografts
Antineoplastic Agents
Neoplasms
Carcinogenesis
Clinical Trials
Apoptosis

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Maher, D. M., Khan, S., Nordquist, J. L., Ebeling, M. C., Bauer, N. A., Kopel, L., ... Chauhan, S. (2015). Ormeloxifene efficiently inhibits ovarian cancer growth. Cancer Letters, 356(2), 606-612. https://doi.org/10.1016/j.canlet.2014.10.009

Ormeloxifene efficiently inhibits ovarian cancer growth. / Maher, Diane M.; Khan, Sheema; Nordquist, Jordan L.; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash.

In: Cancer Letters, Vol. 356, No. 2, 01.01.2015, p. 606-612.

Research output: Contribution to journalArticle

Maher, DM, Khan, S, Nordquist, JL, Ebeling, MC, Bauer, NA, Kopel, L, Singh, MM, Halaweish, F, Bell, MC, Jaggi, M & Chauhan, S 2015, 'Ormeloxifene efficiently inhibits ovarian cancer growth', Cancer Letters, vol. 356, no. 2, pp. 606-612. https://doi.org/10.1016/j.canlet.2014.10.009
Maher DM, Khan S, Nordquist JL, Ebeling MC, Bauer NA, Kopel L et al. Ormeloxifene efficiently inhibits ovarian cancer growth. Cancer Letters. 2015 Jan 1;356(2):606-612. https://doi.org/10.1016/j.canlet.2014.10.009
Maher, Diane M. ; Khan, Sheema ; Nordquist, Jordan L. ; Ebeling, Mara C. ; Bauer, Nichole A. ; Kopel, Lucas ; Singh, Man Mohan ; Halaweish, Fathi ; Bell, Maria C. ; Jaggi, Meena ; Chauhan, Subhash. / Ormeloxifene efficiently inhibits ovarian cancer growth. In: Cancer Letters. 2015 ; Vol. 356, No. 2. pp. 606-612.
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