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A triphenylethylene nonsteroidal SERM attenuates cervical cancer growth

Neeraj Chauhan1,2, Diane M Maher3, Murali M Yallapu1,2

  • 1Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 38163, Memphis, TN, USA.

Scientific Reports
|July 31, 2019
PubMed

Insights

Ormeloxifene, a repurposed drug, shows significant anti-cancer effects against cervical cancer by inhibiting tumor growth and metastasis. This selective estrogen receptor modulator (SERM) offers a promising new therapeutic strategy for this deadly disease.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Cervical cancer remains a significant global health challenge, particularly in advanced stages.
  • Human papillomavirus (HPV) vaccines have advanced prevention, yet effective treatments for metastatic cervical cancer are limited.
  • Repurposing existing drugs like selective estrogen receptor modulators (SERMs) offers a viable strategy for novel therapeutic development.

Purpose of the Study:

  • To investigate the anti-cancer properties of ormeloxifene (ORM), a SERM, in cervical cancer.
  • To explore the molecular mechanisms underlying ORM's efficacy against cervical cancer cells.
  • To evaluate ORM's potential as a therapeutic agent for cervical cancer treatment.

Main Methods:

  • Assessed the effects of ormeloxifene on cervical cancer cell proliferation, migration, and invasion.
  • Analyzed cell cycle progression, apoptosis, and key signaling pathways (PI3K/Akt).
  • Investigated the modulation of HPV oncoproteins (E6/E7) and tumor suppressor proteins (p53, Rb).
  • Evaluated ormeloxifene's efficacy in an orthotopic mouse model and its radio-sensitizing potential.

Main Results:

  • Ormeloxifene significantly attenuated tumorigenic and metastatic properties of cervical cancer cells.
  • ORM induced G1-S cell cycle arrest, apoptosis, and decreased PI3K/Akt phosphorylation.
  • The drug repressed HPV E6/E7 oncoproteins and restored tumor suppressor protein expression.
  • Ormeloxifene demonstrated radio-sensitization and potent tumor growth inhibition in vivo.

Conclusions:

  • Ormeloxifene exhibits significant anti-cancer activity against cervical cancer.
  • ORM's mechanism involves cell cycle arrest, apoptosis induction, and modulation of HPV-related pathways.
  • Ormeloxifene represents a promising, safe, and rapidly translatable therapeutic option for cervical cancer.

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