Dihydroalterperylenol from endophytic fungus Alternaria semiverrucosa and its antitumour activity uncovered by...

Medicinal plants host a variety of endophytic fungi, which produce numerous secondary metabolites with diverse biological activities. The present study identified ten natural compounds isolated from the endophytic fungal strain Alternaria semiverrucosa, derived from Taxus wallichiana var. mairei. The cytotoxicity of all isolated compounds was evaluated against six tumor cell lines. Dihydroalterperylenol (compound 1) exhibited the highest cytotoxicity against HeLa cells (IC50=6.43±3.0 µM). Cells were treated with 0.1% DMSO and 6.0 µmol/l for 24 h, after which total RNA was extracted for transcriptome library construction and sequencing analysis. Transcriptome analysis identified 140 differentially expressed genes (DEGs), including 99 upregulated and 41 downregulated genes. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significant enrichment of these DEGs in the TGFβ signaling pathway and Hippo signaling pathway. Gene ontology analysis indicated that the DEGs were predominantly involved in the regulation of cell proliferation. Notably, reverse transcription‑quantitative PCR validation confirmed the upregulation of three genes (TGIF2, ID1 and BMP2) which was consistent with the transcriptome sequencing results. Additionally, molecular docking and molecular dynamics simulations were employed to explore the molecular mechanisms underlying the antitumor activity of compound 1. The results suggest that compound 1 exerts its anticancer effects in cervical cancer by regulating the expression of genes TGIF2, ID1 and BMP2.