1-Octen-3-ol from Bamboo Leaves Suppresses Lung Squamous Cell Carcinoma Progression by Targeting the PI3K/AKT Pathway and Activating p53/Caspase-3-Dependent Apoptosis.

Lung squamous cell carcinoma (LUSC), a major subtype of non-small cell lung cancer, presents substantial therapeutic challenges due to limited targeted therapy options and prevalent drug resistance. In this study, we characterised 1-octen-3-ol, an active compound derived from bamboo leaves, as a bioactive natural compound with anti-LUSC activity. In vitro, 1-octen-3-ol significantly suppressed LUSC cell proliferation, migration, invasion, and colony formation, while promoting apoptosis. Network pharmacology predicted the PI3K/AKT pathway as a central mediator of its activity. Mechanistic studies confirmed that 1-octen-3-ol inhibited PI3K and AKT phosphorylation, accompanied by increased expression of p53 and cleaved-caspase3. The PI3K agonist 740Y-P and AKT agonist SC79 partially reversed the effects of 1-octen-3-ol on LUSC cell migration, invasion, colony formation, and protein expression, underscoring the critical role of the PI3K/AKT pathway. In vivo, 1-octen-3-ol markedly suppressed LUSC xenograft growth, and its tumor-suppressive effect was abrogated by co-administration of either the PI3K or AKT agonist. This study is the first to demonstrate that 1-octen-3-ol exerts potent inhibition of LUSC progression via modulation of the PI3K/AKT pathway, thereby activating p53 and initiating caspase-3-dependent apoptosis. These findings provide mechanistic insights into the anti-LUSC activity of 1-octen-3-ol, a natural volatile small-molecule, and support further lead-discovery efforts based on natural-product sources.