Jean-François Jeannin
France
Research Article
Activation of Akt by the Mammalian Target of Rapamycin Complex 2 Renders Colon Cancer Cells Sensitive to Apoptosis Induced by Nitric Oxide and Akt Inhibitor
Author(s): Rahamata Ali-Boina, Marion Cortier, Nathalie Decologne, Cindy Racoeur-Godard, Cédric Seignez, Myriam Lamrani, Jean-François Jeannin, Catherine Paul and Ali BettaiebRahamata Ali-Boina, Marion Cortier, Nathalie Decologne, Cindy Racoeur-Godard, Cédric Seignez, Myriam Lamrani, Jean-François Jeannin, Catherine Paul and Ali Bettaieb
Clinical and preclinical studies have shown that inhibition of Akt or mammalian target of rapamycin (mTOR) signaling alone is not sufficient to treat colorectal carcinoma. Recently, the nitric oxide (NO) donor glyceryl trinitrate (GTN) was reported to revert the resistance to anticancer agents. In search of combination therapies, we show here that concomitant treatment with GTN, an Akt inhibitor, triciribine and a non-specific protein kinase A inhibitor, H89 synergistically induced apoptosis of rapamycin-resistant colon cancer cells as evaluated by Hoechst staining. Biochemical analyses as western blotting indicated that treatment of cells with H89 induced activation of Akt and p70S6K1 as attested by their phosphorylation. This effect did not blockade GTN/H89-inducing apoptosis but restrained it since addition of triciribine dramatically enhanced apoptosis. This phenomenal synergistic.. View More»
DOI:
10.4172/2157-2518.S8-004