Biflavonoids from Selaginella doederleinii as Potential Antitumor Agents for Intervention of Non-Small Cell Lung Cancer

Four new biflavonoids (1–4) were isolated from Selaginella doederleinii together with a known biflavonoid derivative (5). Their structures contained a rare linker of individual flavones to each other by direct C-3-O-C-4′′′ bonds, and were elucidated by extensive spectroscopic data, including HRESIMS, NMR and ECD data. All isolates significantly inhibited the proliferation of NSCLC cells (IC50 = 2.3–8.4 μM) with low toxicity to non-cancer MRC-5 cells, superior to the clinically used drug DDP. Furthermore, the most active compound 3 suppressed XIAP and survivin expression, promoted upregulation of caspase-3/cleaved-caspase-3, as well as induced cell apoptosis and cycle arrest in A549 cells. Together, our findings suggest that 3 may be worth studying further for intervention of NSCLC.