biostudies-literatureUnknown20(9)Nam AYNon-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, remaining a significant challenge in terms of early detection, effective treatment, and improving patient survival rates. In this study, we investigated the anticancer mechanism of rubiarbonol B (Ru-B) and its derivative 3-O-acetylrubiarbonol B (ARu-B), a pentacyclic terpenoid in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. Concentration- and time-dependent cytotoxicity was observed for both Ru-B and ARu-B. The in vitro kinase assay showed that ARu-B treatment inhibited epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition (MET), and AKT1, and their phosphorylation in HCC827 cells. A molecular docking model suggested that ARu-B could interact with EGFR and MET in dPloS onee0329706https://www.ebi.ac.uk/biostudies/studies/S-EPMC12416685biostudies-literature3-O-acetylrubiarbonol B preferentially targets EGFR and MET over rubiarbonol B to inhibit NSCLC cell growth.PMC12416685Lee NYYoon GPark JWShim JHNa MNam AYJoo SHfalse3-O-acetylrubiarbonol B preferentially targets EGFR and MET over rubiarbonol B to inhibit NSCLC cell growth.Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, remaining a significant challenge in terms of early detection, effective treatment, and improving patient survival rates. In this study, we investigated the anticancer mechanism of rubiarbonol B (Ru-B) and its derivative 3-O-acetylrubiarbonol B (ARu-B), a pentacyclic terpenoid in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. Concentration- and time-dependent cytotoxicity was observed for both Ru-B and ARu-B. The in vitro kinase assay showed that ARu-B treatment inhibited epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition (MET), and AKT1, and their phosphorylation in HCC827 cells. A molecular docking model suggested that ARu-B could interact with EGFR and MET in d2025-01-01T00:00:00Z20252026-06-03T05:58:30.102Z2026-04-25T03:16:54.736ZS-EPMC124166854092067510.1371/journal.pone.0329706