Fig. 5.

Proposed model for how cAMP‐hydrolyzing PDE inhibitors potentiate statin‐induced cancer cell death. Compounds that increase intracellular cAMP levels, including PDE inhibitors (e.g., dipyridamole, cilostazol) and forskolin, can sensitize cancer cells to statin‐induced apoptosis. Dipyridamole and cilostazol also inhibit statin‐induced activation of SREBP2 through a cAMP‐independent mechanism, which abrogates the restorative feedback loop of the MVA pathway and further sensitizes cancer cells to statin‐induced apoptosis.