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.
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.
Kwon
Kang Beom
KB
Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Korea.
Kim
Eun Kyung
EK
Han
Mi Jeong
MJ
Shin
Byung Cheul
BC
Park
Yong Kweon
YK
Kim
Kang San
KS
Lee
Young Rae
YR
Park
Jin Woo
JW
Park
Byung Hyun
BH
Ryu
Do Gon
DG
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
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9