Acidic fibroblast growth factor overexpression partially protects 3T3 fibroblasts from apoptosis induced by synthetic retinoid CD437

Abstract

Retinoids are proapoptotic compounds with therapeutic potential for treating cancer. We evaluated the apoptotic effect of the novel retinoid CD437, and particularly its relationship to Akt and acidic fibroblast growth factor (aFGF). We hypothesized that the novel synthetic retinoid CD437 would exert its apoptotic effect by reducing the activity of Akt. We further hypothesized that aFGF would protect against CD437 apoptosis by preserving the activity of Akt. Initially we demonstrated that CD437 produces apoptotic cell death in NIH 3T3 fibroblasts, and that this effect is attenuated in fibroblasts transfected to express aFGF. Next we assessed Akt activity and showed that phospho-Akt is significantly reduced in 3T3 cells exposed to CD437. We showed that this effect is less pronounced in aFGF transfected 3T3 cells. Furthermore, we observed that the addition of exogenous aFGF to 3T3 cells significantly increases Akt phosphorylation. These findings tend to confirm our hypothesis that reduction in Akt activation is a mechanism involved in the apoptotic effect of the retinoid CD437, and that preservation of Akt phosphorylation occurs in response to aFGF and appears to explain the partially protective effect of aFGF for 3T3 cells vis a vis CD437.