Herbal prescription, Danggui-Sayuk-Ga-Osuyu-Senggang-Tang, inhibits TNF-α-induced epithelial-mesenchymal transition in HCT116 colorectal cancer cells

Abstract

Tumor necrosis factor‑α‑mediated (TNF‑α) epithelial‑mesenchymal transition (EMT) is associated with distant metastasis in patients with colorectal cancer with poor prognosis. Although traditional herbal medicines have long been used to treat colorectal cancer, the incidence and mortality in patients with colorectal cancer has continued to increase. Danggui‑Sayuk‑Ga‑Osuyu‑Saenggang‑Tang (DSGOST) has long been used for treatment of chills, while few studies have reported its anticancer effect. This study aimed to demonstrate the inhibitory effect of DSGOST on TNF‑α‑mediated invasion and migration of colorectal cancer HCT116 cell lines. MTT was used to measure cell viability. Wound healing and Τranswell invasion assay were used to detect migration and invasion of cells, respectively. The intracellular localization of proteins of interest was assessed by immunocytochemistry. Western blotting was performed to determine the expression level of various proteins. A non‑toxic dose of DSGOST (50 µg/ml) on HCT116 cells was determined by MTT assay. Furthermore, DSGOST prevented the TNF‑α‑induced invasive phenotype in HCT116 cells. DSGOST inhibition of the invasive phenotype was also associated with increased expression of EMT markers. Furthermore, DSGOST treatment blocked TNF‑α‑induced migration and invasion of HCT116 cells. In addition, DSGOST treatment inhibited TNF‑α‑mediated nuclear translocation of Snail. DSGOST treatment also downregulated TNF‑α‑induced phosphorylation of AKT and glycogen synthase kinase‑3β. Therefore, the findings of the current study suggest that DSGOST exhibits anti‑migration and anti‑invasion effects in TNF‑α‑treated HCT116 human colorectal cells.

Protective effects of Cotoneaster integerrimus on in vitro and ex-vivo models of H2 O2 -induced lactate dehydrogenase activity in HCT116 cell and on lipopolysaccharide-induced inflammation in rat colon

“…TNFα has been recently reported to stimulate HCT116 cell migration, in an experimental wound healing test (Lee et al, ).…”

Research Progress on the Relationship Between Inflammation and Colorectal Cancer

“… 75 , 76 In addition, TNF‐α can also trigger the activation of the epithelial–mesenchymal transition (EMT). 77 These characteristics can promote the formation and metastasis of CRC neovascularization. Clinical studies have shown that high levels of TNF‐α expression are found in the bodies of a large number of CRC patients, and TNF‐α levels can be seen to decrease after the removal of the primary tumor, which may be due to the surgical removal of the primary tumor, thereby reducing the stimulation of the immune system and reducing the production of TNF‐α by lymphocytes.…”

“…TNF‐α can induce the expression of genes involved in tumor invasion and metastasis by activating NF‐κB, including adhesion molecules, matrix metallopeptidase 9 (MMP9), cyclooxygenase‐2 (COX‐2), and vascular endothelial growth factor (VEGF) 75,76 . In addition, TNF‐α can also trigger the activation of the epithelial–mesenchymal transition (EMT) 77 . These characteristics can promote the formation and metastasis of CRC neovascularization.…”

MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease

“…To date, a vast number of drugs have been designed against the targeted proteins [32][33][34]. Naturally derived and chemically synthesize inhibitors are used effectively against the targeted proteins [35][36][37][38][39][40][41][42][43]. Irisin has a vital role in various metabolic and neurological problems, indicating its high therapeutic value, so using irisin as a therapeutic agent can be a good strategy for pharmaceutical industries.…”