Vitamin K3 (menadione) suppresses epithelial-mesenchymal-transition and Wnt signaling pathway in human colorectal cancer cells

Publication date: Available online 22 June 2019Source: Chemico-Biological InteractionsAuthor(s): Chandra Kishore, Sandhya Sundaram, Devarajan KarunagaranAbstractTumor recurrence and metastasis decrease the survival rate of colorectal cancer (CRC) patients. Menadione reduces the numbers and incidences of 1,2-dimethylhydrazine induced colon tumors in mouse but the mechanism of anticancer activity of menadione in colorectal cancer is not very clear. Since Wnt signaling is constitutively active in CRC and it aggravates the epithelial mesenchymal transition (EMT), the regulation of EMT and Wnt signaling by menadione (vitamin K3) was investigated in CRC cells. Menadione showed cytotoxicity against human CRC cells (SW480 and SW620) and human primary colon cancer cells but was relatively ineffective against the cells from human normal colon (CRL-1790) and human primary colon epithelial cells. Menadione suppressed invasion, migration and epithelial-mesenchymal transition in human CRC cells by upregulating the expression of E-cadherin (CDH1), ZO-1 and downregulating that of N-cadherin (CDH2), Vimentin (VIM), ZEB1, MMP2 and MMP9. Menadione decreased TOPFlash/FOPFlash luciferase activity and expression of several downstream targets of Wnt signaling and coactivators such as β-catenin (CTNNB1), TCF7L2, Bcl9l, p300 (EP300) and cyclin D1 (CCND1) was suppressed. Menadione induced differentiation and increased apoptotic cell population in SubG0 phase of cell cycle in SW480 and SW620 cel...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research

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Colon cancer (CC) is one of the leading causes of cancer related mortality. Research over past decades have profoundly enhanced our understanding of immunotherapy, a major clinical accomplishment, and its potential role towards treating CC. However, studies investigating the expression of these immune checkpoints, such as epithelial cell adhesion molecule (EpCAM), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1), by peripheral blood mononuclear cells (PBMCs) is lacking. Here, high-dimensional mass cytometry (CyTOF) is used to investigate immune alterations and promising immunotherapeutic targets expression ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Trichostatin A inhibits phenotypic transition and induces apoptosis of the TAF-treated normal colonic epithelial cells through regulation of TGF-β pathway. Int J Biochem Cell Biol. 2019 Jul 03;:105565 Authors: Huang C, Wu XF, Wang XL Abstract Tumor-associated fibroblasts (TAFs) contribute to transdifferentiation of stromal cells in tumor microenvironment. Epithelial-mesenchymal transition (EMT) is a procedure of phenotypic remodeling of epithelial cells and extensively exists in local tumoral stroma. Histone deacetylase (HDAC) inhibitor Tricostatin A (TSA) and sodium butyrate (SB) are reported to...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer. Oncotarget. 2019 Jun 18;10(40):4004-4017 Authors: Witherspoon M, Sandu D, Lu C, Wang K, Edwards R, Yeung A, Gelincik O, Manfredi G, Gross S, Kopelovich L, Lipkin S Abstract Ethylmalonic Encephalopathy Protein 1 (ETHE1) is a sulfur dioxygenase that regulates cellular H2S levels. We previously demonstrated a significant increase of ETHE1 expression in "single-hit" colon epithelial cells from crypts of patients with Familial Adenomatous Polyp...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ConclusionThis study revealed that C. curetum has potential α-amylase, α-glucosidase, porcine pancreatic lipase enzyme inhibitory activity and cytotoxic activity against the HeLa and Colo-205 cancer cell lines, which indicates the presence of biologically active and cytotoxic compounds in this plant species. This may be considered a challenge for developing bioactive compounds in diabetes, obesity and cancer management.
Source: European Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
CONCLUSIONS: Time of day of alcohol intake may be an important determinant of colon tissue damage and carcinogenicity. This article is protected by copyright. All rights reserved. PMID: 31237690 [PubMed - as supplied by publisher]
Source: Alcoholism, Clinical and Experimental Research - Category: Addiction Authors: Tags: Alcohol Clin Exp Res Source Type: research
Abstract Tumor recurrence and metastasis decrease the survival rate of colorectal cancer (CRC) patients. Menadione reduces the numbers and incidences of 1,2-dimethylhydrazine induced colon tumors in mouse but the mechanism of anticancer activity of menadione in colorectal cancer is not very clear. Since Wnt signaling is constitutively active in CRC and it aggravates the epithelial mesenchymal transition (EMT), the regulation of EMT and Wnt signaling by menadione (vitamin K3) was investigated in CRC cells. Menadione showed cytotoxicity against human CRC cells (SW480 and SW620) and human primary colon cancer cells b...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
Prolyl hydroxylase 3 (PHD3) has initially been reported to hydroxylase hypoxia-inducible factor α (HIFα) and mediate HIFα degradation. More recent studies have shown that, in addition to HIFα, PHD3 has also other substrates. Moreover, pHD3 is believed to act as a tumor suppressor, but the underlying mechanism remains to be elucidated. Here, we demonstrate that PHD3 stabilizes p53 in a hydroxylase-independent manner. We found that PHD3 overexpression increases and PHD3 knockdown decreases p53 levels. Mechanistically, PHD3 bound MDM2 proto-oncogene (MDM2) and prevented MDM2 from interacting with p53, ...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Signal Transduction Source Type: research
Enterococcus faecalis strains are resident intestinal bacteria associated with invasive infections, inflammatory bowel diseases, and colon cancer. Although factors promoting E. faecalis colonization of intestines are not fully known, one implicated pathway is a phosphotransferase system (PTS) in E. faecalis strain OG1RF that phosphorylates gluconate and contains the genes OG1RF_12399 to OG1RF_12402 (OG1RF_12399-12402). We hypothesize that this PTS permits growth in gluconate, facilitates E. faecalis intestinal colonization, and exacerbates colitis. We generated E. faecalis strains containing deletions/point mutations in th...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research
Interleukin-17 (IL-17) has been shown to promote development of prostate, colon, skin, lung, breast, and pancreatic cancer. The purpose of this study was to determine if IL-17 regulates MTA1 expression and its biological consequences. Human cervical cancer HeLa and human prostate cancer DU-145 cell lines were used to test if IL-17 regulates metastasis associated 1 (MTA1) mRNA and protein expression using quantitative reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Cell migration and invasion were studied using wound healing assays and invasion chamber assays. Thirty-four human cervi...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: Primary carcinoma with plasmacytoid morphology is a dedifferentiated variant of adenocarcinoma or poorly cohesive carcinomas. Vimentin positive dedifferentiated-poorly cohesive carcinomas should be considered as mesenchymal-type highly malignant carcinomas. This rare histologic variant of gastrointestinal cancer might respond to anti-c-MET tyrosine kinases. PMID: 31205468 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
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