Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein kinase pathway and target cancer stem cells.
Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein kinase pathway and target cancer stem cells.
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DOI：
10.1016/j.bmc.2012.03.002
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发表时间：
2012-05-01
影响因子：
3.5
通讯作者：
Dou, Q. Ping
中科院分区：
文献类型：
--
作者：
Chen, Di;Pamu, Sreedhar;Cui, Qiuzhi;Chan, Tak Hang;Dou, Q. Ping
AMP活化蛋白激酶（AMPK）是细胞能量状态的关键监测因子，还控制与肿瘤发展相关的过程，包括细胞周期进程、蛋白质合成、细胞生长和存活。因此，AMPK作为一个抗癌靶点最近受到了广泛关注。据报道，抗糖尿病药物二甲双胍以及一些天然化合物，如槲皮素、染料木黄酮、辣椒素和绿茶多酚表没食子儿茶素没食子酸酯（EGCG），能够激活AMPK并抑制癌细胞生长。实际上，天然产物一直是开发抗癌药物最有成效的先导来源，但诸如生物利用度低和效力弱等公认的缺点限制了它们在临床上的开发和应用。在这项研究中，我们证明合成的EGCG类似物4和6是比二甲双胍和EGCG更有效的AMPK激活剂。这些EGCG类似物对AMPK的激活导致细胞增殖受到抑制，细胞周期蛋白依赖性激酶抑制剂p21上调，mTOR通路下调，以及人乳腺癌细胞中干细胞群体受到抑制。我们的研究结果表明，可以从天然和合成来源中发现新型高效且特异的AMPK激活剂，它们有潜力用于临床抗癌治疗。
AMP-activated protein kinase (AMPK) is a critical monitor of cellular energy status and also controls processes related to tumor development, including cell cycle progression, protein synthesis, cell growth and survival. Therefore AMPK as an anti-cancer target has received intensive attention recently. It has been reported that the anti-diabetic drug metformin and some natural compounds, such as quercetin, genistein, capsaicin and green tea polyphenol epigallocatechin gallate (EGCG), can activate AMPK and inhibit cancer cell growth. Indeed, natural products have been the most productive source of leads for the development of anti-cancer drugs but perceived disadvantages, such as low bioavailability and week potency, have limited their development and use in the clinic. In this study we demonstrated that synthetic EGCG analogs 4 and 6 were more potent AMPK activators than metformin and EGCG. Activation of AMPK by these EGCG analogs resulted in inhibition of cell proliferation, up-regulation of the cyclin-dependent kinase inhibitor p21, down-regulation of mTOR pathway, and suppression of stem cell population in human breast cancer cells. Our findings suggest that novel potent and specific AMPK activators can be discovered from natural and synthetic sources that have potential to be used for anti-cancer therapy in the clinic.
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DOI：
10.1186/bcr1673
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fillmore C;Kuperwasser C
通讯作者：
Kuperwasser C
DOI：
10.2217/14796694.2.1.83
发表时间：
2006-02-01
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Huang, Haojie;Tindall, Donald J
通讯作者：
Tindall, Donald J
DOI：
10.1080/01635581.2011.523497
发表时间：
2011-01-01
影响因子：
2.9
作者：
Dou, Dan;Ahmad, Aamir;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
3.5
作者：
Huo, Congde;Yang, Huanjie;Cui, Qiuzhi Cindy;Dou, Q. Ping;Chan, Tak Hang
通讯作者：
Chan, Tak Hang
DOI：
10.1006/bbrc.2001.5627
发表时间：
2001-09-21
影响因子：
3.1
作者：
Imamura, K;Ogura, T;Esumi, H
通讯作者：
Esumi, H