C18H17NO6 inhibits proliferation and induces apoptosis in human osteosarcoma U2OS cells via the PI3K/AKT signaling pathway
Year: 2026
Type: article
Abstract: Background: C18H17NO6 is a dibenzofuran derivative of (+)-usnic acid extracted from Usnea lichens. The present study aimed to investigate the effects and potential mechanisms of C18H17NO6 on human osteosarcoma U2OS cells.Methods: U2OS cells were treated with different concentrations of C18H17NO6. Cell proliferation was detected using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined by TdT-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry [FCM; Annexin-V and propidium iodide (PI)], and cell cycle distribution was analyzed by FCM. Protein and messenger RNA (mRNA) expression levels were measured by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). In vivo experiments were performed using a U2OS xenograft mouse model. Additionally, a PI3K agonist (740Y-P) and a PI3K inhibitor (LY294002) were used to verify the involvement of the PI3K/AKT pathway.Results: C18H17NO6 inhibited U2OS cell proliferation in a dose- and time-dependent manner, induced apoptosis, and caused S-phase cell cycle arrest. It downregulated Ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, p-AKT, and p-PI3K, while upregulating Bax, cleaved caspase-3, and cleaved caspase-9. In the xenograft model, C18H17NO6 suppressed tumor growth without significantly affecting body weight or liver/kidney function. p-PI3K and p-AKT were also downregulated in tumor tissues. The PI3K agonist 740Y-P reversed the C18H17NO6-induced downregulation of PI3K/AKT phosphorylation, whereas the PI3K inhibitor LY294002 mimicked the effects of C18H17NO6.Conclusions: C18H17NO6 exerts significant antitumor effects in vitro and in vivo by inhibiting the PI3K/AKT signaling pathway.
Source: Translational Cancer Research
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7224088844