Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway

Abstract

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.

p-Coumaric acid, Kaempferol, Astragalin and Tiliroside Influence the Expression of Glycoforms in AGS Gastric Cancer Cells

“…Their application in cancer treatment gains attention due to their safety, efficiency and low side effects [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Altered glycosylation is also considered as a hallmark of carcinogenesis with involvement in the disease outcome [ 19 ]. Abnormal glycosylation is claimed to be a key factor of tumor malignant transformation and is closely related to the biological behaviors of tumor cells, such as growth, proliferation, migration and invasion [ 13 , 20 ].…”

Ficus dubia Latex Extract Induces Cell Cycle Arrest and Apoptosis by Regulating the NF-κB Pathway in Inflammatory Human Colorectal Cancer Cell Lines

“…In this regard, the inhibitory effect of FDLE on HCT-116 and HT-29 colorectal cancer cell lines and the possible molecular mechanism were explicated. Firstly, TNF-α caused inflammation in cancers was commonly implemented in numerous investigations [ 26 ]. However, there is no evidence for the use of TNF- α and LPS to induce cell proliferation and inflammation in cancer cells.…”

Antifatigue Effect of Panax Notoginseng Leaves Fermented With Microorganisms: In-vitro and In-vivo Evaluation

“…Cells were treated with a water extract of PNL or FPNL for 48 h, and then washed twice with cold PBS. Total cell protein was extracted by RIPA buffer (Beyotime, Shanghai, China), and protein concentrations were assessed by the BCA assay kit (Beyotime, Shanghai, China) ( 29 ). Target protein samples were separated by 10% SDS-PAGE and transferred by electroblotting to polyvinylidene difluoride (PVDF) membranes.…”