Imperatorin, a furanocoumarin from Angelica dahurica (Umbelliferae), induces cytochrome c-dependent apoptosis in human promyelocytic leukaemia, HL-60 Cells.
Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was found to induce apoptosis in human promyelocytic leukaemia, HL-60 cells. DNA fragmentation assay, morphology-based evaluation, and flow cytometric analysis demonstrated that imperatorin at micromolar concentrations was able to trigger apoptosis of HL-60 cells. Neither necrosis nor differentiation was observed at cytotoxic micromolar concentrations of imperatorin. Further studies showed that the cytochrome c/caspase-9 pathway was responsible for imperatorin-induced apoptosis; i.e., mitochondrial membrane was depolarized, Bcl-2 was down-regulated, cytochrome c was released from mitochondria, caspase-9 and caspase-3 were activated, and poly(ADP-ribose) polymerase was cleaved. Furthermore, imperatorin-induced apoptosis was significantly blocked by Z-VAD-FMK (a broad spectrum caspase inhibitor), Z-LEHD-FMK (a caspase-9 inhibitor) and Ac-DMQD-CHO (a caspase-3 inhibitor), but not by Z-IEDT-FMK (a caspase-8 inhibitor).
Pae
Hyun-Ock
HO
Medicinal Resources Research Center of Wonkwang University, Iksan, Chobuk 570-479, South Korea.
Oh
Hyuncheol
H
Yun
Young-Gab
YG
Oh
Gi-Su
GS
Jang
Seon Il
SI
Hwang
Kee-Myoung
KM
Kwon
Tae-Oh
TO
Lee
Ho-Sub
HS
Chung
Hun-Taeg
HT
D029969:Angelica; D017209:Apoptosis; D015153:Blotting, Western; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D011564:Furocoumarins / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D061945:Caspase Inhibitors; D003574:Cytochrome c Group; D011564:Furocoumarins; D020169:Caspases; C031534:imperatorin