title: Resveratrol and quercetin in combination have anticancer activity in colon cancer cells and repress oncogenic microRNA-27a.
abstract: 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.
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Del Follo-Martinez
authors.forename: Nivedita
authors.initials: N
authors.lastname: Banerjee
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Li
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.forename: Susanne
authors.initials: S
authors.lastname: Mertens-Talcott
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D004789:Enzyme Activation; D019073:HT29 Cells; D006801:Humans; D007700:Kinetics; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D016329:Sp1 Transcription Factor / Q000235:genetics; D051705:Sp3 Transcription Factor / Q000235:genetics; D051706:Sp4 Transcription Factor / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C497124:SP4 protein, human; D016329:Sp1 Transcription Factor; D051706:Sp4 Transcription Factor; D013267:Stilbenes; D051705:Sp3 Transcription Factor; D011794:Quercetin; D053148:Caspase 3; D000077185:Resveratrol