title: Effects of polyphenolic anthrone derivatives, resistomycin and hypercin, on apoptosis in human megakaryoblastic leukemia CMK-7 cell line.
abstract: A tetrahydroxyanthrone derivative, resistomycin, was isolated from the culture broth of Streptomyces sulphureus and a similar polyphenolic dianthraquinone, hypericin, was isolated from an extract of Hypericum perforatum L. as modulators for apoptosis. Resistomycin inhibited apoptosis induced by actinomycin D (AD) with or without acceleration by colcemid (CL) in human megakaryoblastic leukemia CMK-7 cells, IC50 for inhibition against AD-induced apoptosis was about 0.5 microM and IC50 for inhibition against AD plus CL-induced apoptosis was about 1 microM. CL alone induced weak apoptosis in cells, which was enhanced by resistomycin. Hypericin did not inhibit AD-induced apoptosis and slightly enhanced CL-induced apoptosis. Emodin, corresponding to 1 of 2 anthraquinone units in hypericin, did not show any effect on this apoptotic system. AD-induced apoptosis was inhibited by the antioxidative flavonoid, luteolin (IC50 45 microM), and a protein kinase C (PKC) inhibitor, staurosporine (IC50 1.5 microM), but these compounds did not affect the CL-induced apoptosis. Hypericin and resistomycin scavenged superoxide anion radicals at the same rate as luteolin. PKC in CMK-7 cells was inhibited by hypericin and luteolin, but not significantly inhibited by resistomycin. This result suggests that the inhibition of AD-induced apoptosis by resistomycin is at least partly correlated with its antioxidative activity, and that the enhancement of CL-induced apoptosis by this compound depends upon the lack of PKC inhibitory activity. Though the mechanism is not clear, the enhancement of the CL-induced apoptosis might be hindered by PKC inhibition in the case of hypericin and luteolin.
authors.affiliation: Research Institute of Biological Resources, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan. y.shiono@aist.go.jp
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shiono
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Shiono
authors.forename: Shujiro
authors.initials: S
authors.lastname: Seo
authors.forename: Syuichi
authors.initials: S
authors.lastname: Oka
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamazaki
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001580:Benzopyrenes / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D003703:Demecolcine / Q000494:pharmacology; D004642:Emodin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007700:Kinetics; D007947:Leukemia, Megakaryoblastic, Acute; D047311:Luteolin; D008958:Models, Molecular; D008968:Molecular Conformation; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification; D011108:Polymers / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000095322:Anthrones
chemical_list: D000873:Anthracenes; D001580:Benzopyrenes; D003609:Dactinomycin; D003703:Demecolcine; D004642:Emodin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D047311:Luteolin; D010569:Perylene; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D011493:Protein Kinase C; D019311:Staurosporine; C018379:resistomycin; C004965:hypericin; C004522:anthrone; D000095322:Anthrones