Effect of evodiamine and berberine on the interaction between DNMTs and target microRNAs during malignant transformation of the colon by TGF-β1

Abstract

The tissue microenvironment functions as a crucial player in carcinogenesis, and transforming growth factor-β1 (TGF-β1) within the microenvironment stimulates the formation of neoplasms. Using an in vitro model of malignancy induced by TGF-β1, we assessed the effect of evodiamine and berberine on the interaction between DNA methyltransferases (DNMTs) and target microRNAs (miRNAs) in the model. Colon tissues from neonatal rats 7 days of age were cultured and malignancy was induced by TGF-β1 in vitro for 48 h, and then the tissues were respectively treated with evodiamine and berberine for 24 h. Morphological alteration of tissues was observed by an inverted microscope, histological structures were observed using hematoxylin and eosin staining, and the expression levels of DNMTs and targeted miRNAs screened by bioinformatics software combined with Gene chip analysis in our previous study were detected by immunohistochemistry and quantified by real-time PCR. Twenty-four hours after treatment with TGF-β1, expression levels of DNMT1, DNMT3A, DNMT3B and miR-152 (target DNMT1), miR-429 (target DNMT3A) and miR-29a (target DNMT3A/3B) were markedly decreased; however, after 48 h, the expression levels of DNMT1 and DNMT3A were significantly increased, but their target miRNAs were still decreased. After treatment with a DNMT inhibitor (5-Aza-dC), expression levels of the miRNAs were increased to a larger extent, but did not reach normal levels. After treatment with berberine and evodiamine for 24 h, respectively, increased expression of DNMT1, DNMT3A, DNMT3B and miR-152, miR-429, miR-29a was noted. In conclusion, the results of the present study suggest that miRNAs can also be post-transcriptionally regulated by their corresponding DNMTs and that berberine and evodiamine regulate the expression of these genes, which provides early epigenetic evidence for the prevention and therapy of colorectal cancer.

BMP9 mediates the anticancer activity of evodiamine through HIF‑1α/p53 in human colon cancer cells

“…In the present study, the effective anticancer activity of Evo, which may be mediated by BMP9 via the upregulation of HIF-1α to partly increase the activity of p53, was demonstrated in human colon cancer. It has been reported that Evo exhibits great anti-cancer activities in many types of cancer, such as tongue, breast, colon, prostate and lung cancer (9)(10)(11)(12)26,27). As far as colon cancer is concerned, the anticancer activity of Evo may be mediated by inactivating the NF-κB (9) or TGF-β1 (11), or activating the p53/p21/Rb pathway (12).…”

“…Evodiamine (Evo), a quinolone alkaloid extracted from traditional herbal medicine Evodia rutaecarpa (7), has multiple pharmacological actions and could be used for obesity, inflammation, infectious and cardiovascular diseases (8). A growing amount of evidence has indicated that Evo exhibits anticancer activity against various types of cancer, such as tongue, colon and breast cancer (9)(10)(11)(12). According to studies, this activity of Evo may be mediated by NF-κB (9), transforming growth factor β1 (TGF-β1) (11) and/or the p53/p21/Rb pathway (12).…”

“…A growing amount of evidence has indicated that Evo exhibits anticancer activity against various types of cancer, such as tongue, colon and breast cancer (9)(10)(11)(12). According to studies, this activity of Evo may be mediated by NF-κB (9), transforming growth factor β1 (TGF-β1) (11) and/or the p53/p21/Rb pathway (12). However, the explicit mechanism underlying this activity requires further exploration.…”

c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis�y expression in response to TGF-β1 in ovarian cancer

“…TGF-β1 is a multifunctional cytokine that regulates cell growth, motility, differentiation, apoptosis and plays an important role in tumor cell proliferation, migration and invasion ( 23 – 25 ). TGF-β1 is frequently overexpressed in multiple malignancies, colorectal ( 26 ), pancreatic ( 27 ), liver ( 28 ) and ovarian cancer ( 29 – 31 ). Canonical TGF-β signaling pathways begin with activation of serine/threonine kinase receptors, followed by the phosphorylation of Smad2/3 and Smad4, which formed into a complex.…”

Preventive and Therapeutic Roles of Berberine in Gastrointestinal Cancers

“…Notably, both BBR and evodiamine increased the expression of DNMT1, DNMT3A, DNMT3B, and their target miRNAs. ese findings suggest that BBR and evodiamine suppress the onset and development of colon cancer by regulating the expression of DNMTs and miRNAs [50].…”