Curcumin protects mesenchymal stem cells against oxidative stress-induced apoptosis via Akt / mTOR / p 70 S 6 K pathway

The application of mesenchymal stem cells (MSCs) for the treatment of ischemic diseases is promising. However, the poor survival of transplanted MSCs has hindered their therapeutic efficacy. Oxidative stress-induced apoptosis is one of the major reasons for their poor survival, while curcumin has the ability to protect cells against oxidative damage. Therefore, we evaluated the effects of curcumin on the survival of MSCs exposed to oxidative stress, and explored its underlying mechanism. Rat bone marrow derived MSCs (BM-MSCs) were treated with various concentrations of hydrogen peroxide (H2O2) or curcumin, or they were exposed to H2O2 after being pre-treated with different concentrations of curcumin for 3 hours. Cell viability was analyzed by ATP assay, flow cytometry and Hoechst 33258 staining. The expression of apoptosis-related proteins and key proteins in the Akt/mTOR/p70S6K pathway were detected by Western blot. Our results showed that H2O2 inhibited the proliferation and survival of BMMSCs in a concentrationand time-dependent manner. H2O2 induced an obvious increase in ratio of Bax/Bcl-2 and expression levels of cleaved caspase-9 and -3. Delightedly, these apoptotic processes could be inhibited or reversed by a pre-incubation with curcumin. We further revealed that the protective effect of curcumin against oxidative injury in BM-MSCs, which could be abolished by Akt inhibitor perifosine, was mediated by elevated phosphorylation of Akt, mTOR and p70S6K. Our data suggest that curcumin is a promising candidate for improving the efficacy of MSCbased therapy for ischemic diseases by activating the Akt/mTOR/p70S6K pathway.