biostudies-literatureUnknown14(6)Ye GNational Natural Science Foundation of ChinaZhejiang Province Natural Science FoundationLung cancer ranks the top of malignancies that cause cancer-related deaths worldwide. The leaves of <i>Morus alba</i> L are traditional Chinese medicine widely applied in respiratory diseases. Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf, but their mechanism of action has still not fully elucidated. We synthesized Moracin N (MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis. MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells. Chemical proteomic results showed that MAN targeted the programmed death ligand 1 (PD-L1) checkpoint pathway and T cell receptor (TCR) signaling pathway, indicating its immune-regulatory function. Cell-Journal of pharmaceutical analysis100926https://www.ebi.ac.uk/biostudies/studies/S-EPMC11226898biostudies-literatureSecondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway.PMC11226898Gao RLi JMai YZhang JYe GSun XfalseSecondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway.Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide. The leaves of <i>Morus alba</i> L are traditional Chinese medicine widely applied in respiratory diseases. Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf, but their mechanism of action has still not fully elucidated. We synthesized Moracin N (MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis. MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells. Chemical proteomic results showed that MAN targeted the programmed death ligand 1 (PD-L1) checkpoint pathway and T cell receptor (TCR) signaling pathway, indicating its immune-regulatory function. Cell-2024-01-01T00:00:00Z2024 Jun2026-05-23T03:13:08.823Z2026-05-23T03:08:12.771ZS-EPMC112268983897452310.1016/j.jpha.2023.12.016