O-desmethylangolensin inhibits the proliferation of human breast cancer MCF-7 cells by inducing apoptosis and promoting cell cycle arrest

被引:13
作者
Choi, Eun Jeong [1 ]
Kim, Gun-Hee [1 ]
机构
[1] Duksung Womens Univ, Plant Resources Res Inst, Seoul 132714, South Korea
基金
新加坡国家研究基金会;
关键词
O-desmethylangolensin; breast cancer; apoptosis; cell cycle arrest; KINASE INHIBITORS; ISOFLAVONES; DAIDZEIN; SOY; PROGRESSION; FLAVONOIDS; PROTEIN; GROWTH; EQUOL; PHYTOESTROGENS;
D O I
10.3892/ol.2013.1601
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of the present study was to investigate the anticancer effect of O-desmethylangolensin (O-DMA) by assessing cell proliferation, apoptosis and cell cycle distribution, as well as exploring the mechanisms underlying these effects in breast carcinoma MCF-7 cells. The cells were exposed to O-DMA (5-200 M) for 24, 48 and 72 h. The results revealed that cell proliferation was significantly inhibited in a dose-dependent manner following treatment for 48 and 72 h, but not after 24 h, and resulted in the significant induction of apoptosis and the promotion of cell cycle arrest at the G(1)/S and G(2)/M phases. To elucidate these effects of O-DMA, the expression levels of cell cycle regulators were measured in the cells exposed to O-DMA at 150 M for 72 h. Of the G(1)/S phase-related proteins, O-DMA modulated the cyclin-dependent kinases (CDKs), with a decrease in CDK2 and CDK4 and an increase in CDK6, and downregulated cyclin D and E. With respect to the G(2)/M-related proteins, O-DMA caused a reduction in CDK1, together with a slight increase in cyclin A and B. In addition, O-DMA downregulated p21(Cip1) and p27(Kip1), but not p16(INK4a) and p15(INK4b), and interacted with the CDK6-cyclin D and CDK1-cyclin B complexes. In conclusion, these results indicate for the first time that the regulation of the CDK4/6-cyclin D and CDK1-cyclin B complexes may participate in the anticancer activity pathway of O-DMA in MCF-7 cells.
引用
收藏
页码:1784 / 1788
页数:5
相关论文
共 32 条
[1]   p21 in cancer: intricate networks and multiple activities [J].
Abbas, Tarek ;
Dutta, Anindya .
NATURE REVIEWS CANCER, 2009, 9 (06) :400-414
[2]   IDENTIFICATION OF LIGNANS AND PHYTOESTROGENS IN URINE OF CHIMPANZEES [J].
ADLERCREUTZ, H ;
MUSEY, PI ;
FOTSIS, T ;
BANNWART, C ;
WAHALA, K ;
MAKELA, T ;
BRUNOW, G ;
HASE, T .
CLINICA CHIMICA ACTA, 1986, 158 (02) :147-154
[3]  
Arai Y, 2000, J Epidemiol, V10, P127
[4]  
Balabhadrapathruni S, 2000, ONCOL REP, V7, P3
[5]   GREATER UNIDIRECTIONAL CALCIUM EFFLUX FROM BONE DURING METABOLIC, COMPARED WITH RESPIRATORY, ACIDOSIS [J].
BUSHINSKY, DA ;
SESSLER, NE ;
KRIEGER, NS .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 262 (03) :F425-F431
[6]   Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1 [J].
Casagrande, F ;
Darbon, JM .
BIOCHEMICAL PHARMACOLOGY, 2001, 61 (10) :1205-1215
[7]   Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by fermented soy milk [J].
Chang, WH ;
Liu, JJ ;
Chen, CH ;
Huang, TS ;
Lu, FJ .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2002, 43 (02) :214-226
[8]   Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells [J].
Choi, Eun Jeong ;
Kim, Gun-Hee .
PHYTOMEDICINE, 2008, 15 (09) :683-690
[9]   Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors [J].
Collins, I ;
Garrett, MD .
CURRENT OPINION IN PHARMACOLOGY, 2005, 5 (04) :366-373
[10]   Genistein inactivates bcl-2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells [J].
Constantinou, AI ;
Kamath, N ;
Murley, JS .
EUROPEAN JOURNAL OF CANCER, 1998, 34 (12) :1927-1934