Comparative Multi-Omics Analysis and Antitumor Activity of <i>Phylloporia crataegi</i> and <i>Phylloporia fontanesiae</i>

Wood-decay fungi, particularly those within the <i>Phylloporia</i> genus, have attracted considerable interest due to their diverse bioactivities, including antitumor, immune-modulatory, anti-inflammatory, antiviral, antioxidant, and antibacterial effects. This study conducted a comparative analysis of the antitumor activities and underlying molecular mechanisms of two <i>Phylloporia</i> species, <i>Phylloporia crataegi</i> and <i>Phylloporia fontanesiae</i>, from Shandong Province. <i>In vitro</i> assays demonstrated that ethanol extract from the two species exhibited significant, time- and concentration-dependent inhibition of breast cancer (MCF-7), esophageal cancer (Eca-109), and human non-small cell lung cancer (A549). Notably, the ethanol extract of <i>P. crataegi</i> (PCCT) displayed the most potent antitumor activity, with the highest inhibition of Eca-109 cells, achieving an IC₅₀ of 1.310 ± 0.052 mg/ml. Metabolomic analysis revealed that <i>P. crataegi</i> contained significantly higher levels of antitumor-associated metabolites, including trans-cinnamic acid, AMP, and 6-phospho-α-D-glucan (<i>P</i> < 0.05). Transcriptomic analysis further indicated that genes involved in cellular stress responses and metabolic pathways were significantly upregulated in <i>P. crataegi</i>, including IRE1-mediated unfolded protein responses, ATPase activity, and calcium signaling pathways, contributing to its antitumor properties. Proteomic analysis corroborated these findings, identifying differentially expressed proteins predominantly associated with secondary metabolite biosynthesis and energy metabolism. This study elucidates the molecular mechanisms underlying the superior antitumor activity of <i>P. crataegi</i>, underscoring the potential of <i>Phylloporia</i> species as valuable resources for drug discovery and therapeutic development.