Reversible inhibition of caspase-3 activity by iron(III) - Potential role in physiological control of apoptosis

Desferoxamine is known to induce apoptosis in cancer cells, but the mechanisms are still not fully understood. We have shown that iron(III) is a potent caspase-3 inhibitor, and the inhibition is reversible by the iron chelating agent desferoxamine. Also, protein disultide isomerase (PDI) is capable of activating caspase-3 inhibited by iron(Ill), likely by formation of iron-sulfur complex through its active site thiols. Data presented here suggests that iron(III) could be a potential inhibitor of apoptosis in vivo, by caspase-3-dependent inhibition with a possibility of recovery through PDI overexpression. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.