Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer is a dynamic process that involves many complex factors, which may explain why a "magic bullet" cure for cancer has not been found. Death rates are still rising for many types of cancers, which possibly contributes to the increased interest in chemoprevention as an alternative approach to the control of cancer. This strategy for cancer control is based on the presumption that because cancer develops through a multi-step process, each step may be a prospective target for reversing or suppressing the process. Thus, the design and development of chemopreventive agents that act on specific and/or multiple molecular and cellular targets is gaining support as a rational approach to control cancer. Nutritional or dietary factors have attracted a great deal of interest because of their perceived ability to act as highly effective chemopreventive agents. They are professed as being generally safe and may have efficacy as chemopreventive agents by preventing or reversing premalignant lesions and/or reducing second primary tumor incidence. Many of these dietary compounds appear to act on multiple target signaling pathways. Some of the most interesting and well documented are resveratrol and components of tea, including EGCG, theaflavins and caffeine. This review will focus on recent work regarding three well-accepted cellular/molecular mechanisms that may at least partially explain the effectiveness of selected food factors, including those indicated above, as chemopreventive anti-promotion agents. These food compounds may act by: (1) inducing apoptosis in cancer cells; (2) inhibiting neoplastic transformation through the inhibition of AP-1 and/or NF-kappaB activation; and/or (3) suppressing COX-2 overexpression in cancer cells.
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PMID:Targeting signal transduction pathways by chemopreventive agents. 1547 50

Epigenetic modifications are involved in cancer pathogenesis, and HDACis are considered potential therapeutic agents. We and others have shown the inhibitory activity of EGCG on HDAC1. But little is known about the effect of EGCG as on epigenetic regulation in cancer. Here, we try to demonstrate that EGCG acts as an HDACi downregulated APP expression, which was pathophysiologically upregulated in cancers and exerts a key role in cancer cell growth. We used PC-12 cells, SK-N-SH cells and primary tumor tissues for our analysis. Male 4-week-old athymic nude mice were used for heterotopic tumor growth assay. We employed Western blotting analysis to detect Bcl-2, Bax, APP, caspase-3, caspase-7, HDAC1 and H4Ac. We used AnnexinV-FITC and TUNEL staining for apoptosis detection. Tumor tissues were examined by immunohistochemical staining. We demonstrated that EGCG suppresses the growth of xenografted adrenal pheochromocytoma. Flow cytometry analysis and TUNEL staining showed that EGCG induced the apoptosis. Treatment with EGCG resulted in decrease in Bcl-2 but increase in Bax and activated caspase-3 and caspase-7. HDAC inhibitor EGCG leaded to hyperacetylated histone H4 by immunofluorescence. EGCG decreased APP levels by immunofluorescence staining and Western blot analysis. Silencing specific to HDAC1 leaded to caspase-3 and caspase-7 activation and cleavage. Our results are the first to demonstrate a functional interaction between EGCG and APP in suppression tumor growth, and provide a new epigenetic effects of EGCG on antitumor.
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PMID:(-)-Epigallocatechin-3-gallate induces cancer cell apoptosis via acetylation of amyloid precursor protein. 2545 72