Epigallocatechin-3-gallate promotes apoptosis in human breast cancer T47D cells through down-regulation of PI3K/AKT and Telomerase

被引:91
|
作者
Moradzadeh, Maliheh [1 ]
Hosseini, Azar [2 ]
Erfanian, Saiedeh [3 ]
Rezaei, Hadi [4 ]
机构
[1] Mashhad Univ Med Sci, Sch Med, Dept New Sci & Technol, Mashhad, Iran
[2] Mashhad Univ Med Sci, Sch Med, Pharmacol Res Ctr Med Plants, Mashhad, Iran
[3] Jahrom Univ Med Sci, Res Ctr Noncommunicable Dis, Jahrom, Iran
[4] Jahrom Univ Med Sci, Dept Microbiol, Jahrom, Iran
关键词
Breast cancer; Epigallocatechin-3-gallate; Telomerase; Apoptosis; PI3K/AKT signaling cascade; TEA POLYPHENOL EPIGALLOCATECHIN-3-GALLATE; GREEN TEA; TAMOXIFEN; GALLATE; PHARMACOKINETICS; CARCINOGENESIS; RATS; CHEMOPREVENTION; PHYTOCHEMICALS; COMBINATION;
D O I
10.1016/j.pharep.2017.04.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Green tea has antioxidant, anti-tumor and anti-bacterial properties. Epigallocatechin-3-gallate (EGCG) in green tea is highly active as a cancer chemopreventive agent. In this study, we designed a series of experiments to examine the effects of EGCG on proliferation and apoptosis of estrogen receptor a-positive breast cancer (T47D) cells. Methods: Cells were treated with EGCG (0-80 mu M) and tamoxifen (0-20 mu M), as the positive control, up to 72 h. Cell viability was determined by MTT assay. Apoptosis investigated by real time PCR of apoptosis and survival (Bax, Bcl-2, p21, p53, PTEN, PI3 K, AKT, caspase3 and caspase9 and hTERT) genes and by western blot of Bax/Bcl-2 proteins expressions. Results: The results showed that EGCG decreased cell viability as concentration-and time-dependently. IC50 values were 14.17 mu M for T47D and 193.10 mM for HFF cells, as compared with 3.39 mu M and 32.75 mu M for tamoxifen after 72 h treatment, respectively. Also, EGCG (80 mM) significantly increased the genes of PTEN, CASP3, CASP9 and decreased AKT approximately equal to tamoxifen. In gene expression, EGCG (80 mM) significantly increased Bax/Bcl-2 ratio to 8-fold vise 15-fold in tamoxifen (20 mu M)-treated T47D cells during 72 h. In protein expression of Bax/Bcl-2, EGCG significantly increased 6-fold while this ratio augmented 10-fold in tamoxifen group. EGCG significantly decreased 0.8, 0.4 and 0.3 gene expression of hTERT in 24, 48 and 72 h, respectively. Conclusions: This study suggests that EGCG may be a useful adjuvant therapeutic agent for the treatment of breast cancer. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.
引用
收藏
页码:924 / 928
页数:5
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