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Yayın Synergistic and dose-dependent effects of pinostrobin, pinocembrin and pinobanksin on different breast cancer cell lines(Kafkas Üniversitesi, 2024) Melekoğlu, Abdullah; Ceviz, Ayşe Begüm; Eronat, Allison Pınar; Öztürk, Tülin; Pehlevan, Funda; Yılmaz-Aydoğan, Hülya; Öztürk, OğuzIn this study, the cytotoxic and apoptotic effects of three phenolic compounds highly found in the poplar type propolis; pinostrobin (PS), pinocembrin (PC) and pinobanksin (PB), were investigated individually and in combination on hormon-positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines and fibrocystic breast epithelium (MCF-10A) as control. Assessment of cytotoxicity and apoptosis were performed with WST-1 and Annexin V-7AAD assays, respectively. All statistical analyses including the two-way ANOVA and multiple-t-test were performed using GraphPad Prism software. Individually, PB (P<0.0001), PS (P<0.0001), and PC (P<0.05) demonstrated potent cytotoxic effects at moderate to high doses and late time intervals on MCF-7. PB and PS have been found to have a significant proliferative effect at low doses (P<0.0001), however, this effect disappeared in higher doses in this cell line. Dual combinations of PB+PC and PB+PS were toxic on MCF-10A, however, dual combination of PS+PC and the triple combination (PB+PS+PC) showed no cytotoxicity until high doses at late time intervals (P>0.05). On MCF-7, the triple combination induced cytotoxic/apoptotic effects even with the 25% dose and 50% dose on MDA-MB-231(p<0.0001). Our findings clearly showed that different combinations of these phenolic substances can have synergistic cytotoxic effects and even hormetic effects in non-tumorogenic cells.