title: Sulfuretin from heartwood of Rhus verniciflua triggers apoptosis through activation of Fas, Caspase-8, and the mitochondrial death pathway in HL-60 human leukemia cells.
abstract: Sulfuretin, a flavonoid isolated from heartwood of Rhus verniciflua, has been reported to have anti-cancer activities but the underlying molecular mechanism was not clear. In this study, sulfuretin induced apoptosis by activating caspases-8, -9, and -3 as well as cleavage of poly(ADP-ribose) polymerase. Furthermore, treatment with sulfuretin caused mitochondrial dysfunctions, including the loss of mitochondrial membrane potential (ΔΨ(m)), the release of cytochrome c to the cytosol, and the translocations of Bax and tBid. Sulfuretin also activated the extrinsic apoptosis pathway, that is, it increased the expressions of Fas and FasL, the activation of caspase-8, and the cleavage of Bid. Furthermore, blocking the FasL-Fas interaction with NOK-1 monoclonal antibody prevented the sulfuretin-induced apoptosis. The therapeutical effect of sulfuretin in leukemia is due to its potent apoptotic activity through the extrinsic pathway driven by a Fas-mediated caspase-8-dependent pathway.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Kyung-Sook
authors.initials: KS
authors.lastname: Chung
authors.forename: Ji-Hyung
authors.initials: JH
authors.lastname: Seo
authors.forename: Sung-Vin
authors.initials: SV
authors.lastname: Yim
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D029045:Rhus / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D053222:Fas Ligand Protein; D005419:Flavonoids; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D053181:Caspase 8; C054989:sulfuretin