title: Induction of apoptosis by Radix Paeoniae Alba extract through cytochrome c release and the activations of caspase-9 and caspase-3 in HL-60 cells.
abstract: Radix Paeoniae Alba has been used as a constituent of herbal medicine prescriptions for the treatment of inflammation, cancer, and other diseases. The aim of this study was to investigate the mechanism of Radix Paeoniae Alba extract (RPAE)-induced apoptosis in HL-60 leukemic cells. We observed that RPAE induced apoptotic changes in a dose-dependent manner, which was confirmed by DNA fragmentation and poly-(ADP-ribose) polymerase (PARP) cleavage. We also found release of cytochrome c from mitochondria to the cytosol in RPAE-treated HL-60 cells. The caspases, caspase-9 and -3, but not caspase-8, were found to be activated in response to RPAE treatment, and the caspase-3 inhibitor, Ac-DEVD-CHO, and the caspase-9 inhibitor, z-LEHD-FMK, but not the caspase-8 inhibitor, z-IETD-FMK, attenuated RPAE-induced DNA fragmentation and PARP cleavage. These results suggest that RPAE-induced apoptosis is stimulated by the release of cytochrome c to the cytosol, by procaspase-9 processing, and via a caspase-3 dependent mechanism.
authors.affiliation: Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Korea.
authors.forename: Kang Beom
authors.initials: KB
authors.lastname: Kwon
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Han
authors.forename: Byung Cheul
authors.initials: BC
authors.lastname: Shin
authors.forename: Yong Kweon
authors.initials: YK
authors.lastname: Park
authors.forename: Kang San
authors.initials: KS
authors.lastname: Kim
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Byung Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Do Gon
authors.initials: DG
authors.lastname: Ryu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D029596:Paeonia / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9