Resveratrol and
quercetin (RQ) in combination (1:1 ratio) previously inhibited growth in human
leukemia cells. This study investigated the anticancer activity of the same mixture in HT-29
colon cancer cells. RQ decreased the generation of
reactive oxygen species (ROS) by up to 2.25-fold and increased the
antioxidant capacity by up to 3-fold in HT-29 cells (3.8-60 μg/mL), whereas IC50 values for viability were 18.13, 18.73, and 11.85 μg/mL, respectively. RQ also induced caspase-3-cleavage (2-fold) and increased PARP cleavage. Specificity
protein (
Sp) transcription factors are overexpressed in colon and other
cancers and regulate genes required for cell proliferation survival and angiogenesis. RQ treatment decreased the expression of Sp1, Sp3, and Sp4
mRNA and this was accompanied by decreased
protein expression. Moreover, the Sp-dependent antiapoptotic survival gene
survivin was also significantly reduced, both at
mRNA and
protein levels. RQ decreased
microRNA-27a (miR-27a) and induced zinc finger
protein ZBTB10, an Sp-repressor, suggesting that interactions of RQ with the miR-27a-ZBTB10-axis play a role in Sp downregulation. This was confirmed by transfection of cells with the specific mimic for miR-27a, which partially reversed the effects of RQ. These findings are consistent with previous studies on botanical
anticancer agents in
colon cancer cells.