Centchroman inhibits proliferation of head and neck cancer cells through the modulation of PI3K/mTOR pathway

Biochem Biophys Res Commun. 2011 Jan 7;404(1):40-5. doi: 10.1016/j.bbrc.2010.11.049. Epub 2010 Nov 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / enzymology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Centchroman / pharmacology*
  • DNA Damage / drug effects
  • Estrogen Antagonists / pharmacology*
  • Head and Neck Neoplasms / enzymology*
  • Humans
  • Phosphoinositide-3 Kinase Inhibitors*
  • STAT3 Transcription Factor / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*


  • Estrogen Antagonists
  • Phosphoinositide-3 Kinase Inhibitors
  • STAT3 Transcription Factor
  • Centchroman
  • TOR Serine-Threonine Kinases