Kaempferol induces apoptosis in human HCT116 colon cancer cells via the Ataxia-Telangiectasia Mutated-p53 pathway with the involvement of p53 Upregulated Modulator of Apoptosis

被引:83
作者
Li, Wei [1 ]
Du, Bingna [1 ]
Wang, Tianyi [1 ]
Wang, Siling [2 ]
Zhang, Jinghai [1 ]
机构
[1] Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Biochem Lab, Shenyang 110016, Peoples R China
[2] Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China
关键词
Colorectal cancer p53; ATM (Ataxia-Telangiectasia Mutated); Kaempferol; PUMA (p53 Upregulated Modulator of Apoptosis); Apoptosis; NEGATIVE PROGNOSTIC-FACTOR; STRAND BREAK REPAIR; COLORECTAL-CANCER; DIETARY FLAVONOIDS; DNA-DAMAGE; LOW BAX; INHIBITION; GROWTH; PROLIFERATION; RISK;
D O I
10.1016/j.cbi.2008.10.048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dietary flavonols have been found to possess preventive and therapeutic potential against several kinds of cancers. This study is conducted to investigate the anti-proliferation effects of kaempferol, a major component of food flavonols. against colon cancer cells. In the human HCT116 colon cancer cell line, kaempferol induced p53-dependent growth inhibition and apoptosis. Furthermore, kaempferol was found to induce cytochrome c release from mitochondria and activate caspase-3 cleavage. The Bcl-2 family proteins including PUMA were involved in this process. Kaempferol also induced ATM and H2AX phosphorylation in HCT116 cells, inhibition of ATM by a chemical inhibitor resulted in abrogation of the downstream apoptotic cascades. These findings Suggest kaempferol could be a potent candidate for colorectal cancer management. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:121 / 127
页数:7
相关论文
共 43 条
[1]   Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas [J].
Anti, M ;
Armuzzi, A ;
Morini, S ;
Iascone, E ;
Pignataro, G ;
Coco, C ;
Lorenzetti, R ;
Paolucci, M ;
Covino, M ;
Gasbarrini, A ;
Vecchio, FM ;
Gasbarrini, G .
GUT, 2001, 48 (02) :238-246
[2]  
Arai Y, 2000, J NUTR, V130, P2243
[3]  
Awwad RA, 2003, CANCER RES, V63, P4731
[4]   Enhanced phosphorylation of p53 by ATN in response to DNA damage [J].
Banin, S ;
Moyal, L ;
Shieh, SY ;
Taya, Y ;
Anderson, CW ;
Chessa, L ;
Smorodinsky, NI ;
Prives, C ;
Reiss, Y ;
Shiloh, Y ;
Ziv, Y .
SCIENCE, 1998, 281 (5383) :1674-1677
[5]   DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis [J].
Bartkova, J ;
Horejsi, Z ;
Koed, K ;
Krämer, A ;
Tort, F ;
Zieger, K ;
Guldberg, P ;
Sehested, M ;
Nesland, JM ;
Lukas, C ;
Orntoft, T ;
Lukas, J ;
Bartek, J .
NATURE, 2005, 434 (7035) :864-870
[6]  
BEDI A, 1995, CANCER RES, V55, P1811
[7]   Kaempferol induced inhibition of HL-60 cell growth results from a heterogeneous response, dominated by cell cycle alterations [J].
Bestwick, Charles S. ;
Milne, Lesley ;
Duthie, Susan J. .
CHEMICO-BIOLOGICAL INTERACTIONS, 2007, 170 (02) :76-85
[8]   Dietary flavonoids and colorectal adenoma recurrence in the polyp prevention trial [J].
Bobe, Gerd ;
Sansbury, Leah B. ;
Albert, Paul S. ;
Cross, Amanda J. ;
Kahle, Lisa ;
Ashby, Jason ;
Slattery, Martha L. ;
Caan, Bette ;
Paskett, Electra ;
Iber, Frank ;
Kikendall, James Walter ;
Lance, Peter ;
Daston, Cassandra ;
Marshall, James R. ;
Schatzkin, Arthur ;
Lanza, Elaine .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2008, 17 (06) :1344-1353
[9]   Disruption of p53 in human cancer cells alters the responses to therapeutic agents [J].
Bunz, F ;
Hwang, PM ;
Torrance, C ;
Waldman, T ;
Zhang, YG ;
Dillehay, L ;
Williams, J ;
Lengauer, C ;
Kinzler, KW ;
Vogelstein, B .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (03) :263-269
[10]   Docosahexaenoic acid induces proteasome-dependent degradation of β-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2 [J].
Calviello, Gabriella ;
Resci, Federica ;
Serini, Simona ;
Piccioni, Elisabetta ;
Toesca, Amelia ;
Boninsegna, Alma ;
Monego, Giovanni ;
Ranelletti, Franco O. ;
Palozza, Paola .
CARCINOGENESIS, 2007, 28 (06) :1202-1209