In vitro antiproliferative activity on A549 and HT-29 cell lines and fatty acid profiling of Agaricus bresadolanus and A. hortensis.

The rising global burden of cancer has intensified the search for novel anticancer agents derived from natural sources, with mushrooms emerging as a rich source of bioactive metabolites. This study provides the first comparative evaluation of the toxic A. bresadolanus and the edible A. hortensis in terms of their fatty acid methyl ester (FAME) profiles and antiproliferative effects against human lung (A549) and colon (HT-29) carcinoma cell lines, alongside cytotoxicity toward normal 3T3 fibroblasts. GC–MS analysis revealed distinct lipid compositions between the two species, with A. hortensis exhibiting higher levels of unsaturated fatty acids (linoleic and oleic acids), whereas A. bresadolanus was enriched in sterol derivatives such as Δ7,22-ergostadienol. Both extracts inhibited cancer cell proliferation in a dose-dependent manner; however, A. hortensis demonstrated greater selectivity, preserving higher fibroblast viability relative to A. bresadolanus. The observed correlation between unsaturated fatty acid content and selective cytotoxicity suggests that lipid composition may contribute to the antitumor potential of mushroom extracts, though further studies are needed to establish causality. These findings identify A. hortensis as a candidate for further investigation as a source of lipid-derived bioactive compounds in future in vivo studies and provide a biochemical basis for the rational selection of Agaricus species in nutraceutical and pharmacological applications.