Combination Effects of Polyphenols Present in Sugarcane on Proliferation in MCF-7 Human Breast Cancer Cells

Sugarcane is one of the most important crops in the world and rich in polyphenols. In this study, quercetin, apigenin, luteolin, tricin and p-coumaric acid, the major polyphenols in sugarcane, were used to evaluate the antiproliferative activities toward MCF-7 human breast cancer cells independently and in combination. These five polyphenols all showed inhibitory effects against MCF-7 cells within different dose ranges. The combinations of luteolin and three polyphenols (quercetin, apigenin, p-coumaric acid) were studied. p-Coumaric acid together with luteolin exhibited synergistic effects at all concentrations tested: the CI (Combination Index) values at 50%, 75% and 90% inhibition of MCF-7 cell growth were 0.68 +/- 0.06, 0.70 +/- 0.08 and 0.83 +/- 0.09, respectively. Although the two-way combination of luteolin and apigenin showed moderate antagonistic effect (CI, 1.26 +/- 0.24) at EC50, the CI value dropped as the inhibition rate increased, showing a synergistic effect at the inhibition rate above 70%. The combination of luteolin and quercetin indicated antagonistic effect at the inhibition rate above 50% (Fa(0.5,) CI = 1.10 +/- 0.05). p-Coumaric acid with quercetin exhibited antagonistic actions (Fa(0.5,) CI = 1.62 +/- 0.22) at all concentrations tested. In addition, the EC50 values of luteolin and quercetin against MCF-7 cells decreased by 1.91 and 2.62-fold after combining with 20 mu M tricin. The results provide evidence of synergistic relation among polyphenols present in sugarcane in inhibition of cancer cell growth and of their potential clinical application.