Dracorhodin Perchlorate Induces Apoptosis via Activation of Caspases and Generation of Reactive Oxygen Species

• Published in: Journal of Pharmacological Sciences Vol. 95; no. 2; pp. 273 - 283
• Main Authors: Xia, Mingyu, Wang, Dong, Wang, Minwei, Tashiro, Shin-ichi, Onodera, Satoshi, Minami, Mutsuhiko, Ikejima, Takashi
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2004; The Japanese Pharmacological Society; Elsevier
• Subjects: Antimetabolites, Antineoplastic - pharmacology; Apoptosis - drug effects; Bax; bcl-2-Associated X Protein; Bcl-XL; Benzopyrans - pharmacology; Blotting, Western; caspase; Caspase Inhibitors; Caspases - metabolism; Cell Line, Tumor; DNA - genetics; DNA - isolation & purification; dracorhodin perchlorate; Enzyme Activation - drug effects; Enzyme Activators - pharmacology; Fluorouracil - pharmacology; HeLa Cells; Humans; Indicators and Reagents; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Monocytes - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; reactive oxygen species; Reactive Oxygen Species - metabolism; Bax; Bcl-XL; dracorhodin perchlorate; reactive oxygen species; caspase
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.fpj03102x

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-XL, 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-XL and Bax protein expression, and induces apoptosis through caspase pathways in HeLa cells.