Integrated in silico and experimental methods revealed that Arctigenin inhibited angiogenesis and HCT116 cell migration and invasion through regulating the H1F4A and Wnt/β-catenin pathway

Abstract

Arctigenin (ARG) has been previously reported to exert diverse biological activities including anti-proliferation, anti-inflammatory, and antiviral, etc. In the current study, the anti-metastasis and anti-angiogenesis activities of ARG were investigated. To further understand how ARG played these bioactivities, proteomic approaches were used to profile the proteome changes in response to ARG treatment using 2DE-MS/MS. Using these approaches, a total of 50 differentially expressed proteins were identified and clustered. Bioinformatics analysis suggested that multiple signalling pathways were involved. Moreover, ARG induced anti-metastatic and anti-angiogenesis activities were mainly accompanied by a deactivation of the Wnt/β-catenin pathway in HCT116 cells.

The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression

“…as little as 10 µM arctigenin exerting significant inhibition and complete inhibition with 200 µM arctigenin. This is in accordance with the anti-migratory capacity of arctigenin previously reported by Zhang et al (15), where 5 µM arctigenin was found to inhibit cell migration in human colon cancer cell lines.…”

“…The other metastatic protease uPA was also inhibited by arctigenin, whereas the uPAR levels remained unchanged. Zhang et al (15) have previously reported the inhibition of cell migration and invasion via the Wnt/β-catenin pathway in human colon cancer cells. They also showed that arctigenin inhibited MMP-9 along with MMP-2.…”

“…Several studies have shown that arctigenin possesses therapeutic effects for anti-viral (2-4), anti-inflammatory (5,6), immune modulatory (7-10) and antitumor activities. Particularly, the antitumor activity of arctigenin has drawn much scientific interest and it has been tested in various human cancer cell lines, showing promising results in cancer cells of the stomach (11,12), liver (12), pancreas (13,14), intestine (15)(16)(17), lung (12,18,19), bladder (20) and ovaries (21). Regarding the effects of arctigenin in breast cancers, Hsieh et al (22) showed that arctigenin markedly inhibited the growth of ER-negative MDA-MB-231 cells by triggering the mitochondrial caspase-independent apoptotic pathway.…”

“…It was reported that 30-75% of patients undergoing surgery and adjuvant treatment developed recurrent metastatic disease and the median survival of patients with metastatic breast cancer is approximately 2 years (29,30). Zhang et al (15) reported that arctigenin inhibited HCT116 colon cancer cell migration and invasion through the regulation of the H1F4A and Wnt/β catenin pathways. However, to the best of our knowledge, the anti-metastatic effect of arctigenin has not been clearly evaluated on breast cancer cells to date.…”

Arctigenin inhibits prostate tumor growth in high-fat diet fed mice through dual actions on adipose tissue and tumor

“…Angiogenesis is critically important for the growth of solid tumors, and tumors will remain in dormant phase for a long time in absence of blood vessel formation 20,21 . The anti-angiogenic activity of arctigenin was also observed in previous studies associated with the inhibition of tumor growth and invasion 30,31 . Tumor angiogenesis is significantly enhanced in obese state, mainly due to the elevated circulating pro-angiogenic/-inflammatory factors released from adipocytes, such as VEGF, IGF-1, MCP-1, IL-1, TNF, etc 24 .…”