Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells.
In our study, luteolin has shown its apoptosis-inducing potent in HL-60 cells with its 76.5% apoptotic ratio of 100 microM treatment. When HL-60 cells were treated with 60 microM of luteolin, DNA ladders were visible at 6 h and increased from 6-12 h after treatment. Luteolin could decrease the mitochondrial membrane potential, trigger cytochrome c released to cytosol, and subsequently induce the processing of procaspase-9 and procaspase-3, which were followed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45). The cleavage of the proapoptotic Bcl-2 proteins, such as Bad and Bax to produce their truncated forms, and the cleavage of the antiapoptotic Bcl-2 proteins, such as Bcl-2 and Bcl-XL, into their potent pro-apoptotic fragments were detected in our study. From the results, we suggested that the structure of luteolin contributes to its potent in inducing apoptosis in HL-60 cells, and the mitochondrial pathway might play an important role in the luteolin-induced apoptosis. The induction of apoptosis by luteolin may offer a pivotal mechanism for its cancertherapeutic and chemopreventive action.
Cheng
An-Chin
AC
Department of Food Science, National Pingtung University, 912, Pingtung, Taiwan.
Huang
Tzou-Chi
TC
Lai
Ching-Shu
CS
Pan
Min-Hsiung
MH
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000009:adverse effects* / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D047309:Flavones; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases