Cytotoxicity and antiproliferative activity of Arctium lappa extract on an in vitro model of human colorectal cancer

Background : Natural remedies are an excellent source for screening innovative and safe anti-cancer medicines. This study is intended to explore the potential toxicity of burdock seed extract, Arctium lappa (A. lappa), as well as its anti-regenerative and anti-proliferative effects on tumor cells in vitro. Methods: The antiproliferative effect of A. lappa ethanol extract (EtOH) was evaluated on human colorectal carcinoma (H-COLO-205) cells and normal skin fibroblast (HSF) cell lines using the SRB assay. Matrix metalloproteinases (MMP-2 and MMP-9) and apoptotic gene expressions (e.g., BAX, BCL-2, P53) were analyzed using Western blot and qRT-PCR, respectively. Results: A. lappa inhibited H-COLO-205 cell growth with an IC₅₀ of 11.80 µg/mL while sparing normal HSF cells (IC₅₀ = 1485 µg/mL). The extract significantly increased pro-apoptotic gene expression, with upregulation of caspase-3 (4.07-fold), caspase-9 (3.66-fold), P53 (2.69-fold), and BAX (22.44-fold), and downregulated the anti-apoptotic gene BCL-2 by 13.33-fold. Migration assays showed that A. lappa reduced MMP-2 and MMP-9 protein levels by 1.36-fold and 1.34-fold, respectively. The extract also downregulated NF-κB expression and significantly decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α. Furthermore, A. lappa enhanced DNA fragmentation, with a 4.36% increase in comet tail migration and an 18.88 tail moment at a 100 µg/mL concentration. Molecular docking revealed that arctigenin, a major compound in A. lappa, forms stabilizing hydrogen bonds with TGF-βR1, inhibiting its kinase function and associated cancer pathways. Conclusion: These results indicate that A. lappa may serve as a promising plant-derived anticancer medication for colon cancer.