title: Dracorhodin perchlorate induces apoptosis via activation of caspases and generation of reactive oxygen species.
abstract: 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.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Xia
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Minwei
authors.initials: M
authors.lastname: Wang
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.forename: Mutsuhiko
authors.initials: M
authors.lastname: Minami
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
chemical_list: D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; D001578:Benzopyrans; D061945:Caspase Inhibitors; D020536:Enzyme Activators; D007202:Indicators and Reagents; D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C060327:dracorhodin; D004247:DNA; D020169:Caspases; D005472:Fluorouracil