(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to inhibit the Wnt/β-catenin pathway, which is aberrantly up-regulated in colorectal cancers, but its precise mechanism of action remains unclear. Here, we used a sensitive cell-based system to demonstrate that EGCG suppresses β-catenin response transcription (CRT), activated by Wnt3a-conditioned medium (Wnt3a-CM), by promoting the degradation of intracellular β-catenin. EGCG induced β-catenin N-terminal phosphorylation at the Ser33/37 residues and subsequently promoted its degradation; however, this effect was not observed for oncogenic forms of β-catenin. Pharmacological inhibition or depletion of glycogen synthase kinase-3β (GSK-3β) did not abrogate the EGCG-mediated β-catenin degradation. EGCG did not affect the activity and expression of protein phosphatase 2A (PP2A). Consistently, the phosphorylation and degradation of β-catenin was found in adenomatous polyposis coli (APC) mutated colon cancer cells after EGCG treatment. EGCG repressed the expression of cyclin D1 and c-myc, which are β-catenin/T-cell factor-dependent genes, and inhibited the proliferation of colon cancer cells. Our findings suggest that EGCG exerts its cancer-preventive or anticancer activity against colon cancer cells by promoting the phosphorylation and proteasomal degradation of β-catenin through a mechanism independent of the GSK-3β and PP2A.
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http://dx.doi.org/10.1002/biof.1185 | DOI Listing |
Chempluschem
December 2024
Centre for Inorganic Chemistry, Chemistry, Bv 120, e/ 60 y 64, Nº1465, 1900, La Plata, ARGENTINA.
The redox imbalance, caused by depletion or generation of reactive oxygen species (ROS), is a key mechanism by which metal complexes exert anticancer effects. Carbidopa has shown the ability to inhibit the MDA-MB-231 cell line, a highly aggressive triple-negative human breast adenocarcinoma, by inducing reductive stress. The metal complex of carbidopa with zinc (ZnCarbi) was designed to modify carbidopa's structure and exhibited increased cytotoxicity against MDA-MB-231 cells.
View Article and Find Full Text PDFTech Coloproctol
December 2024
Department of Faculty Surgery No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Background: Reduced-port laparoscopic surgery (RPLS) uses the minimum possible number of ports or small-sized ports in laparoscopic surgery. The combination of RPLS and natural orifice specimen extraction (NOSE) minimizes the procedural damage.
Methods: A total of 17 patients diagnosed with right colon cancer were included: 5 patients in the RPLS + NOSE group and 12 patients in the conventional laparoscopic surgery (CL) + mini-laparotomy (ML) group.
Cancer Chemother Pharmacol
December 2024
Departments of Pharmacology, Medicine Faculty, Sivas Cumhuriyet University, Sivas, Türkiye.
Purpose: Human epidermal growth factor-2 (HER-2) targeted drugs are used in only HER-2 overexpressed cancers. However, only a small portion of these cancer types are HER-2 overexpressed. In this study, we aimed to upregulate HER-2 receptors in MCF-7 breast cancer and HT-29 colon cancer cell cultures, which these cells are not HER-2 upregulated in natural status.
View Article and Find Full Text PDFmBio
December 2024
Molecular Biology Institute, University of California, Los Angeles, California, USA.
Unlabelled: Many bacteria metabolize ethanolamine as a nutrient source through cytoplasmic organelles named bacterial microcompartments (BMCs). Here we investigated the molecular assembly, regulation, and function of BMCs in a Gram-negative oral pathobiont that is associated with adverse pregnancy outcomes. The genome harbors a conserved ethanolamine utilization () locus with 21 genes that encode several putative BMC shell proteins and a two-component signal transduction system (TCS), in addition to the enzymes for ethanolamine transport and catabolism.
View Article and Find Full Text PDFDalton Trans
December 2024
Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany.
Chemotherapy is one of the most widely used anticancer treatments worldwide. However, despite its clinical effectiveness, most chemotherapeutic agents are associated with severe side effects. To address this limitation, there is an urgent need for the development of novel anticancer agents.
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