Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells

被引:65
作者
Cheng, AC
Huang, TC
Lai, CS
Pan, MH
机构
[1] Natl Kaohsiung Marine Univ, Dept Seafood Sci, Kaohsiung, Taiwan
[2] Natl Pingtung Univ, Dept Food Sci, Pingtung 912, Taiwan
[3] Shuzen Coll Med & Management, Dept Phys Therapy, Kaohsiung, Taiwan
关键词
luteolin; apoptosis; caspase; mitochondria; Bcl-2; Bcl-X-L; bad; bax; cleavage;
D O I
10.1016/j.ejphar.2004.12.026
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In our study, luteolin has shown its apoptosis-inducing potent in HL-60 cells with its 76.5% apoptotic ratio of 100 muM treatment. When HL-60 cells were treated with 60 muM 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-X-L, 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. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 10
页数:10
相关论文
共 39 条
[1]  
ARENDS MJ, 1991, INT REV EXP PATHOL, V32, P223
[2]   Antiapoptotic herpesvirus Bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins [J].
Bellows, DS ;
Chau, BN ;
Lee, P ;
Lazebnik, Y ;
Burns, WH ;
Hardwick, JM .
JOURNAL OF VIROLOGY, 2000, 74 (11) :5024-5031
[3]   Dietary agents in cancer prevention: flavonoids and isoflavonoids [J].
Birt, DF ;
Hendrich, S ;
Wang, WQ .
PHARMACOLOGY & THERAPEUTICS, 2001, 90 (2-3) :157-177
[4]   Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals [J].
Cai, QY ;
Rahn, RO ;
Zhang, RW .
CANCER LETTERS, 1997, 119 (01) :99-107
[5]  
Chen CW, 1996, INT J ONCOL, V9, P811
[6]   Conversion of Bcl-2 to a Bax-like death effector by caspases [J].
Cheng, EHY ;
Kirsch, DG ;
Clem, RJ ;
Ravi, R ;
Kastan, MB ;
Bedi, A ;
Ueno, K ;
Hardwick, JM .
SCIENCE, 1997, 278 (5345) :1966-1968
[7]   Apoptotic signaling pathways: Caspases and stress-activated protein kinases [J].
Cho, SG ;
Choi, EJ .
JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2002, 35 (01) :24-27
[8]   Modulation of cell death by Bcl-xL through caspase interaction [J].
Clem, RJ ;
Cheng, EHY ;
Karp, CL ;
Kirsch, DG ;
Ueno, K ;
Takahashi, A ;
Kastan, MB ;
Griffin, DE ;
Earnshaw, WC ;
Veliuona, MA ;
Hardwick, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) :554-559
[9]   Antioxidant properties of hydroxy-flavones [J].
Cotelle, N ;
Bernier, JL ;
Catteau, JP ;
Pommery, J ;
Wallet, JC ;
Gaydou, EM .
FREE RADICAL BIOLOGY AND MEDICINE, 1996, 20 (01) :35-43
[10]  
Crozier A, 2000, BIOL RES, V33, P79