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<p>As a major agricultural residue, spent mushroom substrate (SMS) holds significant potential for valorization. Current strategies primarily focus on agricultural recycling and the extraction of bioproducts, notably polysaccharides. In contrast, the pharmacological potential of other bioactive constituents, such as sterols, remains largely unexplored. This study presents an integrated multi-omics strategy to elucidate the high-value utilization pathway of SMS from <i>Inocutis levis</i> by investigating the bioactivity of its petroleum ether extract (SYM) against human esophageal cancer Eca-109 cells as a model system. GC–MS analysis revealed that sterols were the main compounds present in SYM. SYM significantly inhibited cell proliferation with a half maximal inhibitory concentration (IC<sub>50</sub>) of 97.865 ± 3.735&#xa0;µg/mL and induced apoptosis, and cell cycle arrest at the G2/M phase. KEGG enrichment analysis based on network pharmacology predicted the MAPK signaling pathway as one of the primary targets. Transcriptomic profiling revealed suppression of MAPK signaling, activation of apoptotic pathways, and induction of endoplasmic reticulum (ER) stress. Metabolomic analysis indicated that SYM treatment impacted metabolites involved in gap junction signaling and nucleotide metabolism related pathways.These findings highlight the potential of SMS-derived bioactive metabolites and suggest their value in the sustainable utilization of agricultural resources.</p> Graphical Abstract <p></p>

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In Vitro Antitumor Activity and Mechanism of Extracts from the Spent Mushroom Substrate of Inocutis Levis

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Yuyue Zhang,
  • Xuan Wu,
  • Ranran Hou,
  • Ting Gao,
  • Guoli Zhang,
  • Xuemei Tian

摘要

As a major agricultural residue, spent mushroom substrate (SMS) holds significant potential for valorization. Current strategies primarily focus on agricultural recycling and the extraction of bioproducts, notably polysaccharides. In contrast, the pharmacological potential of other bioactive constituents, such as sterols, remains largely unexplored. This study presents an integrated multi-omics strategy to elucidate the high-value utilization pathway of SMS from Inocutis levis by investigating the bioactivity of its petroleum ether extract (SYM) against human esophageal cancer Eca-109 cells as a model system. GC–MS analysis revealed that sterols were the main compounds present in SYM. SYM significantly inhibited cell proliferation with a half maximal inhibitory concentration (IC50) of 97.865 ± 3.735 µg/mL and induced apoptosis, and cell cycle arrest at the G2/M phase. KEGG enrichment analysis based on network pharmacology predicted the MAPK signaling pathway as one of the primary targets. Transcriptomic profiling revealed suppression of MAPK signaling, activation of apoptotic pathways, and induction of endoplasmic reticulum (ER) stress. Metabolomic analysis indicated that SYM treatment impacted metabolites involved in gap junction signaling and nucleotide metabolism related pathways.These findings highlight the potential of SMS-derived bioactive metabolites and suggest their value in the sustainable utilization of agricultural resources.

Graphical Abstract