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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / physiology
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Caco-2 Cells
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Cell Cycle Checkpoints / drug effects*
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Cell Cycle Checkpoints / physiology
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Cell Nucleus / metabolism
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Colonic Neoplasms* / drug therapy
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Colonic Neoplasms* / enzymology
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Colonic Neoplasms* / pathology
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G1 Phase / drug effects
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G1 Phase / physiology
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Gene Expression Regulation, Enzymologic / drug effects
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Glucuronates / metabolism
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Glucuronosyltransferase / genetics*
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Glucuronosyltransferase / metabolism
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Humans
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Isothiocyanates
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NF-E2-Related Factor 2 / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Resting Phase, Cell Cycle / drug effects
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Resting Phase, Cell Cycle / physiology
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Sulfoxides
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Thiocyanates / pharmacology*
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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BAX protein, human
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Glucuronates
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Isothiocyanates
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NF-E2-Related Factor 2
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NFE2L2 protein, human
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Proto-Oncogene Proteins c-bcl-2
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Sulfoxides
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Thiocyanates
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bcl-2-Associated X Protein
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UGT1A1 enzyme
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bilirubin uridine-diphosphoglucuronosyl transferase 1A10
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Glucuronosyltransferase
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UDP-glucuronosyltransferase, UGT1A8
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sulforaphane