Imperatorin, a Furanocoumarin from Angelica dahurica (Umbelliferae), Induces Cytochrome c‐Dependent Apoptosis in Human Promyelocytic Leukaemia, HL‐60 Cells
2002; Wiley; Volume: 91; Issue: 1 Linguagem: Inglês
10.1034/j.1600-0773.2002.910107.x
ISSN1600-0773
AutoresHyun‐Ock Pae, Hyuncheol Oh, Young‐Gab Yun, Gi‐Su Oh, Seon Il Jang, Kee‐Myoung Hwang, Tae‐Oh Kwon, Ho Sub Lee, Hun‐Taeg Chung,
Tópico(s)Cancer therapeutics and mechanisms
ResumoAbstract: 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).
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