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 anticancer 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 IC(50 )of 11.80 mu g/mL while sparing normal HSF cells (IC50 = 1485 mu g/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-KB expression and significantly decreased the levels of inflammatory cytokines IL-6, IL-1/3, and TNF-a. Furthermore, A. lappa enhanced DNA fragmentation, with a 4.36% increase in comet tail migration and an 18.88 tail moment at a 100 mu g/mL concentration. Molecular docking revealed that arctigenin, a major compound in A. lappa, forms stabilizing hydrogen bonds with TGF-/3R1, 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.