title: Centchroman inhibits proliferation of head and neck cancer cells through the modulation of PI3K/mTOR pathway.
abstract: Centchroman (CC; 67/20; INN: Ormeloxifene) is a non-steroidal antiestrogen extensively used as a female contraceptive in India. In the present study, we report the anti-proliferative effect of CC in head and neck squamous cell carcinoma (HNSCC) cells. CC inhibited cell proliferation in a dose dependent manner at 24 h of treatment. Further studies showed that CC treatment induced apoptosis, inhibited Akt/mTOR and signal transducers and activators of transcription protein 3 (STAT3) signaling, altered proteins associated with cell cycle regulation and DNA damage and inhibited colony forming efficiency of HNSCC cells. In addition, CC displayed anti-proliferative activity against a variety of non-HNSCC cell lines of diverse origin. The ability of CC to serve as a dual-inhibitor of Akt/mTOR and STAT3 signaling warrants further studies into its role as a therapeutic strategy against HNSCC.
authors.affiliation: Department of Radiotherapy, C.S.M. Medical University, Lucknow, Uttar Pradesh 226003, India.
authors.forename: Vikas Kumar
authors.initials: VK
authors.lastname: Srivastava
authors.forename: Rishi Kumar
authors.initials: RK
authors.lastname: Gara
authors.forename: M L B
authors.initials: ML
authors.lastname: Bhatt
authors.forename: D P
authors.initials: DP
authors.lastname: Sahu
authors.forename: Durga Prasad
authors.initials: DP
authors.lastname: Mishra
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002486:Centchroman / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004965:Estrogen Antagonists; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050796:STAT3 Transcription Factor; D002486:Centchroman; D058570:TOR Serine-Threonine Kinases