Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1

Isaam Ben Sahra, Claire Regazzetti, Guillaume Robert, Kathiane Laurent, Yannick Le Marchand-Brustel, Patrick Auberger, Jean François Tanti, Sophie Giorgetti-Peraldi, Frédéric Bost*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

447 Scopus citations


Metformin is a widely prescribed antidiabetic drug associated with a reduced risk of cancer. Many studies show that metformin inhibits cancer cell viability through the inhibition of mTOR. We recently showed that antiproliferative action of metformin in prostate cancer cell lines is not mediated by AMP-activated protein kinase (AMPK). We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin. We show that metformin increases REDD1 expression in a p53-dependent manner. REDD1 invalidation, using siRNA or REDD1 -/- cells, abrogates metformin inhibition of mTOR. Importantly, inhibition of REDD1 reverses metformin-induced cell-cycle arrest and significantly protects from the deleterious effects of metformin on cell transformation. Finally, we show the contribution of p53 in mediating metformin action in prostate cancer cells. These results highlight the p53/REDD1 axis as a new molecular target in anticancer therapy in response to metformin treatment.

Original languageEnglish (US)
Pages (from-to)4366-4372
Number of pages7
JournalCancer Research
Issue number13
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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