title: Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells.
abstract: Sulforaphane (SFN), a naturally occurring chemopreventive and anticancer agent, is a nuclear factor, erythroid 2-like 2 (NFE2L2/Nrf2) inducer. Nrf2 plays a critical role in coordinating the cell defense system by initiating the transcription of cytoprotective genes, including detoxification enzymes such as NAD(P)H quinone dehydrogenase 1 (NQO1) and transport proteins such as ATP-binding cassette, subfamily C (CFTR/MRP). Recently, the essential role of Nrf2 in tumor development and progression and in the development of multidrug resistance in cancer cells has been highlighted. The aim of this study was to compare the effect of SFN on the Nrf2 system and the Nrf2-target enzymes NQO1 and MRP in human untransformed epithelial colon CRL-1790 cells and in HT-29 and Caco-2 colorectal cancer cells to elucidate the role of SFN in cancer prevention and treatment. We have demonstrated that SFN has excellent cytoprotective properties in CRL-1790 cells, as it induced Nrf2-dependent expression of MRP1 and NQO1. SFN induced Nrf2 target enzyme activity in HT-29 and Caco-2 cancer cells but regulated the Nrf2/ARE signaling pathway differently in cancer and untransformed cells.
authors.affiliation: a Department of Cell Biology , National Medicines Institute , Warszawa , Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lubelska
authors.affiliation: a Department of Cell Biology , National Medicines Institute , Warszawa , Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wiktorska
authors.affiliation: a Department of Cell Biology , National Medicines Institute , Warszawa , Poland.|b Department of Bioanalysis and Analysis of Drugs , Medical University of Warsaw , Warszawa , Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Mielczarek
authors.affiliation: a Department of Cell Biology , National Medicines Institute , Warszawa , Poland.|c Chair and Department of Synthesis and Chemical Technology of Pharmaceutical Substances , Medical University of Lublin , Lublin , Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Milczarek
authors.affiliation: a Department of Cell Biology , National Medicines Institute , Warszawa , Poland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Zbroińska-Bregisz
authors.affiliation: a Department of Cell Biology , National Medicines Institute , Warszawa , Poland.|d Institute of Nursing and Health Sciences, University of Rzeszów , Rzeszów , Poland.
authors.forename: Zdzisław
authors.initials: Z
authors.lastname: Chilmonczyk
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D013454:Sulfoxides; D015262:Xenobiotics / Q000493:pharmacokinetics
chemical_list: D016588:Anticarcinogenic Agents; D004798:Enzymes; D017879:Isothiocyanates; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016660:NAD(P)H Dehydrogenase (Quinone); D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D015262:Xenobiotics; C495635:NFE2L2 protein, human; C447479:NQO1 protein, human; C016766:sulforaphane; C421109:multidrug resistance-associated protein 1