Cytotoxicity of <i>Dysphania botrys</i> L. Extracts Against HEPG2 and SAOS‐2, In Vitro and In Silico

ABSTRACT Cancer is a leading cause of mortality worldwide, and plants natural products are known to be safer sources of anticancer agents. Dysphania botrys , is a plant traditionally used against gastrointestinal infections, anti‐inflammatory purposes and as spice. This study was designed to investigate the anticancer potential of D. botrys . The hexane and methanol–chloroform extracts were prepared by maceration of the crushed air‐dried plant material sequentially in the solvents. GC–MS/MS and LC–ESI–MS/MS were used to identify phytochemical constituents in the extracts and their antiproliferative properties were assessed against liver (HEPG2) and bone (SAOS‐2) cancer cell lines by MTT assay. Endothelial HUVEC cells were used to assess selectivity and cytotoxicity. In addition, in silico methods such as DFT, MEP, molecular docking, MD and MM–PBSA were performed on major compounds. In the GC–MS/MS analysis, palmitic, linoleic, oleic and stearic acids were detected in the hexane extract, while LC–ESI–MS/MS analysis revealed that the methanol–chloroform extract was rich in phenolic and polyphenolic compounds, including trans ‐ferulic acid, vanillic acid, sinapic acid, trans ‐cinnamic acid and resveratrol as the major components. MTT assay demonstrated time‐dependent antiproliferative effects of both extracts. The methanol–chloroform extract exhibited notable IC 50 values: 39.30–14.56 (24–48 h, HEPG2); 61.96–28.32 (24–48 h, SAOS‐2), and no cytotoxicity was observed up to 93.09 µg/mL on HUVEC (normal cells). The IC 50 values were comparable to those of the reference drug 5‐fluorouracil, but with significantly reduced toxicity towards normal cells. According to the results of molecular docking, resveratrol was identified as the most effective antiproliferative molecule, and this was confirmed by MD and MM–PBSA. Therefore, D. botrys is a potential source of anticancer phytomedicine against liver and bone cancer that requires further investigations.