title: Combination of quercetin and hyperoside has anticancer effects on renal cancer cells through inhibition of oncogenic microRNA-27a.
abstract: Quercetin and hyperoside (QH) in combination (1:1 ratio) have previously been shown to inhibit the growth of human leukemia cells. Here, we investigated the anticancer activity of the same mixture in 786-O renal cancer cells. QH 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 786-O cells (3.8-60 μg/ml), whereas IC50 values for viability were 18.2, 18.7 and 11.8 μg/ml, respectively. QH also induced caspase-3 cleavage (2-fold) and increased PARP cleavage. Specificity protein (Sp) transcription factors are overexpressed in cancer cells and regulate genes required for cell proliferation, survival and angiogenesis. QH treatment decreased the expression of Sp1, Sp3 and Sp4 mRNA and this was accompanied by decreased protein expression. Moreover, expression of the Sp-dependent anti-apoptotic survival gene survivin was also significantly reduced, both at the mRNA and protein levels. QH decreased microRNA-27a (miR-27a) and induced the zinc finger protein ZBTB10, an Sp-repressor, suggesting that interactions between QH and the miR-27a-ZBTB10 axis play a role in Sp downregulation. This was confirmed by transfection of cells with a specific mimic for miR-27a, which partially reversed the effects of QH. These findings are consistent with previous studies on botanical anticancer agents in colon cancer cells.
authors.affiliation: Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Che
authors.forename: Guang-Chun
authors.initials: GC
authors.lastname: Wang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor / Q000096:biosynthesis; D051705:Sp3 Transcription Factor / Q000096:biosynthesis; D051706:Sp4 Transcription Factor / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C497121:SP3 protein, human; C497124:SP4 protein, human; D016329:Sp1 Transcription Factor; D051706:Sp4 Transcription Factor; C559929:ZBTB10 protein, human; D051705:Sp3 Transcription Factor; C021304:hyperoside; D011794:Quercetin; D053148:Caspase 3