title: Effects of phytochemicals sulforaphane on uridine diphosphate-glucuronosyltransferase expression as well as cell-cycle arrest and apoptosis in human colon cancer Caco-2 cells.
abstract: Our study investigated the effects of the chemopreventive agent sulforaphane (SFN) on human colon cancer Caco-2 cells and potential underlying mechanisms of the effects.  When treated with SFN at  hypotoxic  levels,  UDP-glucuronosyltransferase  1A  (UGT1A)  was  induced  in  a  dose-dependent manner.  SFN at 25  μM showed the highest UGT1A-induction activity, inducing UGT1A1, UGT1A8, and UGT1A10 mRNA expression, and increasing UGT-mediated N-hydroxy-PhIP glucuronidation.  SFN- induced UGT1A expression may have resulted from Nrf2 nuclear translocation or activation.  At higher concentrations, e.g. 75  μM, SFN caused G1/G2 cell cycle arrest and induced apoptosis possibly through reducing anti-apoptotic bcl-2 expression and increasing apoptosis-inducing bax expression in Caco-2 cells.  Taken together, these results demonstrated the chemopreventive effects of SFN on human colon cancer Caco-2 cells may have been partly attributed to Nrf2-mediated UGT1A induction and apoptosis induction, and our studies provided theoretic and experimental basis for clinical application of SFN to human colon cancer prevention.
authors.affiliation: Department of Geriatrics and Gastroenterology, Qi-Lu Hospital of Shandong University Key Laboratory of Proteomics of Shandong Province, Jinan Shandong, People's Republic of China. doctorminmin@163.com
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Defeng
authors.initials: D
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Yang
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018938:Caco-2 Cells; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000099148:UGT1A1 Enzyme
chemical_list: D005965:Glucuronates; D014453:Glucuronosyltransferase; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D019253:Proto-Oncogene Proteins c-bcl-2; D013454:Sulfoxides; D013861:Thiocyanates; D051028:bcl-2-Associated X Protein; D000099148:UGT1A1 Enzyme; C494826:BAX protein, human; C495635:NFE2L2 protein, human; C476725:bilirubin uridine-diphosphoglucuronosyl transferase 1A10; C454320:UDP-glucuronosyltransferase, UGT1A8; C016766:sulforaphane