Unveiling the Anticancer Potential of <i>Verbascum aydogdui</i> : Isolation, Characterization, and In Vitro Studies

Cytotoxic activity-guided fractionation of the ethanolic extract of Verbascum aydogdui, an endemic halophyte plant to Türkiye, resulted in the isolation of 16 secondary metabolites, including eight triterpene saponins, mulleinsaponins III (1), ilwensisaponin A (2), buddlejasaponin I (3), mulleinsaponin IV (4), ilwensisaponins D (5), ilwensisaponin C (6), craniosaponin A (7) and buddlejasaponin Ia (8), six iridoid glycosides, aucubine (9), eurostoside (10), geniposidic acid (11), nigroside III (13), 6-O-β-D-glucopyranosylaucubine (12), 6-O-[3-O-(E-feruloyl)-α-L-rhamnopyranosyl]-aucubine (14), and two phenylethanoid glycosides, verbascoside (15) and alyssonoside (16). Compounds 1-5 displayed significant cytotoxicity against PC3, HEPG2, HGC27, A375, MCF7, and SW480 cancer cell lines with half-maximal inhibitory concentration values of 17.6-85.1 µM, being 2 and 3 the most cytotoxic ones. Thus, 2 and 3 were further assayed for their cell death mechanisms, including apoptosis and necrosis. Compound 2 exerted anti-cancer effects in all cancer cell lines tested, except for MCF7, especially via inducing apoptosis. Its apoptotic activity was predominantly mediated by a significant increase in p53 and p21 expressions in all cancer lines tested, but for SW480. This is the first bioactivity and phytochemical study on V. aydogdui. Our results indicated that 2 could be a potential anticancer natural product that merits further in vitro and in vivo studies.