A triphenylethylene nonsteroidal SERM attenuates cervical cancer growth

Neeraj Chauhan, Diane M. Maher, Murali Yallapu, Bilal Hafeez, Man M. Singh, Subhash Chauhan, Meena Jaggi

Research output: Contribution to journalArticle

Abstract

Selective estrogen receptor modulator drug molecules of triphenylethylene family have gained considerable attention as anti-cancer agents. Despite recent advances in screening and development of HPV vaccines, cervical cancer remains one of the deadliest malignancies as advanced stage metastatic disease is mostly untreatable, thus warrants newer therapeutic strategies. Ormeloxifene (ORM) is a well-known SERM of triphenylethylene family that has been approved for human use, thus represents an ideal molecule for repurposing. In this study, we for the first time have demonstrated the anti-cancerous properties of ormeloxifene in cervical cancer. Ormeloxifene efficiently attenuated tumorigenic and metastatic properties of cervical cancer cells via arresting cell cycle at G1-S transition, inducing apoptosis, decreasing PI3K and Akt phosphorylation, mitochondrial membrane potential, and modulating G1-S transition related proteins (p21, cyclin E and Cdk2). Moreover, ORM repressed the expression of HPV E6/ E7 oncoproteins and restored the expression of their downstream target tumor suppressor proteins (p53, Rb and PTPN 13). As a result, ormeloxifene induces radio-sensitization in cervical cancer cells and caused potent tumor growth inhibition in orthotopic mouse model. Taken together, ormeloxifene represents an alternative therapeutic modality for cervical cancer which may have rapid clinical translation as it is already proven safe for human use.

Original languageEnglish (US)
Article number10917
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Selective Estrogen Receptor Modulators
Uterine Cervical Neoplasms
Growth
Tumor Suppressor Protein p53
Papillomavirus Vaccines
Cyclin E
Neoplasms
Mitochondrial Membrane Potential
Oncogene Proteins
Radio
Phosphatidylinositol 3-Kinases
ormeloxifene
triphenylethylene
Cell Cycle
Phosphorylation
Apoptosis
Therapeutics
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

A triphenylethylene nonsteroidal SERM attenuates cervical cancer growth. / Chauhan, Neeraj; Maher, Diane M.; Yallapu, Murali; Hafeez, Bilal; Singh, Man M.; Chauhan, Subhash; Jaggi, Meena.

In: Scientific reports, Vol. 9, No. 1, 10917, 01.12.2019.

Research output: Contribution to journalArticle

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