Multi-omics analysis reveals inhibition of osteosarcoma progression by sporoderm-removed Ganoderma lucidum spores via targeting glycerophospholipid and fatty acid metabolism
Abstract Osteosarcoma (OS) is a severe malignancy affecting children and adolescents, with limited effective treatments leading to poor outcomes. This study explored the potential of sporoderm-removed Ganoderma lucidum spores (RGLS) as a novel therapeutic agent against OS and elucidated its mechanis...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-05890-5 |
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| Summary: | Abstract Osteosarcoma (OS) is a severe malignancy affecting children and adolescents, with limited effective treatments leading to poor outcomes. This study explored the potential of sporoderm-removed Ganoderma lucidum spores (RGLS) as a novel therapeutic agent against OS and elucidated its mechanism of action. Our in vivo and in vitro experiments showed that RGLS significantly inhibited S-180 OS cell proliferation, while simultaneously inducing apoptosis. Multi-omics analysis revealed that RGLS disrupted glycerophospholipid metabolism by upregulating lysophosphatidylcholine (LysoPC) levels through phospholipase A2 (PLA2)-mediated pathways. Co-culture assays further demonstrated that RGLS promoted the endocytosis of macrophage-derived Pla2g7 protein into S-180 cells, enhancing its anti-cancer effects. Additionally, RGLS modulated the cellular fatty acid profile and suppressed the β-oxidation of long-chain fatty acids, leading to energy depletion in OS cells. These findings provide a novel view of the multi-targeted mechanisms of RGLS, positioning it as a promising candidate for OS therapy. |
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| ISSN: | 2045-2322 |