Mechanism of inhibitory effect of sodium orthovanadate on DNA damage-induced apoptosis

Abstract

We investigated the mechanism of sodium orthovandate (vanadate)-mediated inhibition of the caspase cleavage of p42/SETβ to p41 in ionizing radiation-induced apoptotic cell death of MOLT-4. We found that vanadate suppressed caspase activation and the subsequent cell death, but it did not suppress caspase activity. We further investigated the effects of vanadate, compared with that of a caspase inhibitor or overexpressing Bcl-2. Consequently, like Bcl-2, the effects are attributed to suppressions of the release of proapoptotic molecules from mitochondria, loss of mitochondrial membrane potential, and Bax conformational change, while the latter two apoptotic events are not suppressed by a caspase inhibitor. Our findings indicate that vanadate acts on upstream event(s) of caspase activation and mitochondrial permeabilization by different way from a caspase inhibitor.