Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

Abstract

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

Arctigenin induces apoptosis in human hepatoblastoma cells

“…Polyphyllin D induced apoptosis and necrosis in cells in a caspase-dependent manner as we reported previously [11]. Arctigenin also induced apoptosis in lung cancer, breast cancer, gallbladder cancer, hepatocellular carcinoma, and colorectal cancer cells [5][6][7][8][9][10]. We thus examined whether arctigenin similarly induces apoptosis in hepatoblastoma cells through caspase activation.…”

“…It is a component of the herbal medicines, Saikoseikanto, which is often used to treat neurosis in children, chronic tonsillitis, eczema, chronic gastrointestinal disorders, and neurosis in weak constitution, and Kufugedokusan, which is effective against sore throat, tonsillitis, and peritonsillitis. In addition, the anti-tumor effect of arctigenin on cell lines derived from lung cancer, breast cancer, gallbladder cancer, colorectal cancer, and hepatocellular carcinoma cases has been reported, but not on those from hepatoblastomas [5][6][7][8][9][10]. In addition to its anti-tumor effects, arctigenin is thought to possess diverse properties, including anti-influenza, anti-inflammatory/analgesic, and anti-hypertension [12][13][14].…”

“…The results of our experiment indicated that necroptosis occurred in a cell line with the MYCN gene, while apoptosis occurred in a cell line lacking the MYCN gene [11]. Although the pathways mediating the antitumor effect of arctigenin are different in various tumors, apoptosis induction occurs in all tumors [5][6][7][8][9][10]. Exogenous apoptosis is initiated with the detection of an extracellular stress signal by a specific intramembrane/extramembrane receptor [15].…”

“…Arctigenin, the main ingredient of Goboshi, i.e., burdock seeds, has been reported to exhibit antitumor effects against lung cancer, breast cancer, gallbladder cancer, hepatocellular carcinoma, colorectal cancer, etc. [5][6][7][8][9][10]. We examined the anti-tumor effects of arctigenin 1 Pediatric Surgery Department, Fujita Health University, Toyoake, Japan in the hepatoblastoma cell line HUH-6 clone 5 (hereinafter, referred to as HUH-6).…”

Recent Progress on the Molecular Mechanisms of Anti-invasive and Metastatic Chinese Medicines for Cancer Therapy

“…Arctigenin can induce anoikis via MAPKs signaling, inhibit EMT through increasing E-cadherin and decreasing N-cadherin, vimentin, β-catenin, and Snail, and downregulate MMP-2/9, so that inhibition on the tumor cell migration and invasion both in vitro and in vivo was achieved [81]. Imperatorin, an active furanocoumarin component obtained from the root of Angelica dahurica, has been demonstrated to sensitize anoikis by downregulating Mcl-1 protein and upregulating Bax in lung cancer [82].…”