Dracorhodin perchlorate induces apoptosis via activation of caspases and generation of reactive oxygen species.

Dracorhodin perchlorate inhibited proliferation of several tumor cell lines. The drug induced oligonucleosomal fragmentation of DNA in HeLa cells and increased caspase-3, -8, -9 activities followed by the degradation of caspase-3 substrates, inhibitor of caspase-dependent DNase, and poly-(ADP-ribose) polymerase. It also increased caspase-1 activity and a caspase-1 inhibitor, Ac-YVAD-cmk, and a caspase-10 inhibitor z-AEVD-fmk, also reduced dracorhodin-perchlorate-induced HeLa cell death. Dracorhodin perchlorate decreased the expression of anti-apoptotic mitochondrial protein, Bcl-X(L), but not Bcl-2; and it increased the expression of pro-apoptotic protein, Bax. Dracorhodin perchlorate induced a sustained generation of reactive oxygen species (ROS) in HeLa cells; caspase-1 inhibitor, Ac-YVAD-cmk, and caspase-3 inhibitor, z-DEVD-fmk, attenuated the generation of ROS. Taken together, our results indicate that dracorhodin perchlorate alters the intracellular redox status, changed the balance of Bcl-X(L) and Bax protein expression, and induces apoptosis through caspase pathways in HeLa cells.