báo cáo khoa học: Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis

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báo cáo khoa học: " Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis"Alshatwi Journal of Experimental & Clinical Cancer Research 2010, 29:167http://www.jeccr.com/content/29/1/167 RESEARCH Open AccessCatechin hydrate suppresses MCF-7 proliferationthrough TP53/Caspase-mediated apoptosisAli A Alshatwi Abstract Catechin hydrate (CH), a strong antioxidant that scavenges radicals, is a phenolic compound that is extracted from plants and is present in natural food and drinks, such as green tea and red wine. CH possesses anticancer poten- tial. The mechanism of action of many anticancer drugs is based on their ability to induce apoptosis. In this study, I sought to characterize the downstream apoptotic genes targeted by CH in MCF-7 human breast cancer cells. CH effectively kills MCF-7 cells through induction of apoptosis. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and real-time PCR assays. Cells were exposed to 150 μg/ml CH and 300 μg/mL CH for 24 hours, which resulted in 40.7% and 41.16% apoptotic cells, respectively. Moreover, a 48-hour exposure to 150 μg/ml CH and 300 μg/ml CH resulted in 43.73% and 52.95% apoptotic cells, respectively. Interestingly, after 72 hours of exposure to both concentrations of CH, almost 100% of cells lost their integrity. These results were further confirmed by the increased expression of caspase-3,-8, and -9 and TP53 in a time-depen- dent and dose-dependent manner, as determined by real-time quantitative PCR. In summary, the induction of apoptosis by CH is affected by its ability to increase the expression of pro-apoptotic genes such as caspase-3, -8, and -9 and TP53.Introduction The modulation of signal transduction pathways, inhi-Catechin compounds including (-)- epigallocatechin-3- bition of cell proliferation, induction of apoptosis, inhi-gallate (EGCG), (-)- epigallocatechin (EGC), epicatechin- bition of tumor invasion and inhibition of angiogenesis3-gallate (ECG) and (p)catechin [1] have been shown to are mechanisms that have been established as inhibit-exhibit cytostatic prope rties in many tumor models ing carcinogenesis [10,11]. These potentially beneficial[2,3]. In addition, the growth of new blood vessels effects of green tea are at tributed to catechin com-required for tumor growth has been prevented by green pounds, particularly EGCG, which is the most abun-tea [4]. In Asian countries, a number of epidemiological dant and extensively studied catechin compound ofobservations have suggested that the low incidence of green tea [12,13].some cancers is due to the consumption of green tea The overall medicinal effects of green tea observed[2,3]. Moreover, epidemiological observations have sug- thus far, are focused on combined activities of severalgested that the consumption of green tea inhibits compounds in green tea rather than that of a singlegrowth of many tumor types [5,6]. compound. In addition, most studies have investigated Breast cancer is the most common cancer and is the the different synergistic bioactivities of all compoundsleading cause of death for women worldwide [7]. Sev- present in tea extracts or have been focused mainly oneral epidemiological observations have suggested that the role of EGCG. Therefore, the present study wasincreased consumption of green tea is related to designed to elucidate the role of the anticancer activityimproved prognosis of human breast cancer [2] and of single compound i.e. CH (Figure 1) at the molecularthat the low risk of breast cancer is associated with level.the intake of green tea in Asian-Americans [8,9]. Materials and methods Catechin Hydrate-A compound of CatechinsCorrespondence: alialshatwi@gmail.comMolecular Cancer Biology Research Lab (MCBRL), Dept. of Food Science and Catechin is a polyphenolic flavonoid which has been iso-Nutrition, College of Agriculture and Food Sciences, King Saud University, lated from a variety of natural sources including teaSaudi Arabia © 2010 Alshatwi; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Alshatwi Journal of Experimental & Clinical Cancer Research 2010, 29:167 Page 2 of 9http://www.jeccr.com/content/29/1/167 Briefly, MCF-7 cells (2 × 104 cells/well) were plated in 96-well pl ...