Lipoxygenase Inhibitory Activity and Prostate Cancer Cytotoxicity of In Situ- and In Vitro-Cultivated Balkan Endemic Sideritis scardica Griseb

<i>Sideritis scardica</i> Griseb., a Balkan endemic species traditionally used for respiratory conditions and wound-healing, was investigated for its 15-lipoxygenase (15-LOX) inhibitory and cytotoxic activities in relation to its phenolic composition. Aerial parts from the wild-collected and in vitro-cultivated plant were successively extracted with hexane, chloroform, and methanol and the methanol extract was further fractionated into ethyl acetate, butanol, and water fractions. This study presents the first combined evaluation of LOX inhibition and cytotoxicity against prostate cell lines WPMY-1 (normal epithelial fibroblast/myofibroblast), PC-3 (epithelial adenocarcinoma, Grade IV), and LNCaP (epithelial carcinoma) and detailed phytochemical profiles of wild-collected and in vitro-cultivated <i>S. scardica</i>. The phytochemical analysis revealed distinct profiles: increased LOX-inhibition activity was related to a higher phenylethanoid/flavone glycoside ratio, while PC cytotoxicity was rather related to flavone glycoside domination in the plant preparations. The cytotoxic effect of the in vitro-obtained preparations was characterized by a marked selectivity when comparing their effects on WPMY-1, PC-3 and LNCaP cells. To our knowledge, this is the first report linking phenylethanoid/flavone glycoside profiles of in situ and in vitro <i>S. scardica</i> plants with dual LOX-inhibitory and anti-prostate cancer activities, supporting the plant's potential as a sustainable source of bioactive compounds.