Synergistic and Dose-Dependent Effects of Pinostrobin, Pinocembrin and Pinobanksin on Different Breast Cancer Cell Lines

Abstract

In 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.