Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B1
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Sulforaphane.pdf
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Author(s)
Techapiesancharoenkij, Nirachara
Navasumrit, Panida
Groopman, John D.
Ruchirawat, Mathuros
Fiala, Jeanette LouiseAllen
Croy, Robert G
Wogan, Gerald N
Essigmann, John M
Date Issued
November 2014
Journal
Toxicology and Applied Pharmacology
Publisher
Elsevier
Citation
Techapiesancharoenkij, Nirachara et al. “Sulforaphane, a Cancer Chemopreventive Agent, Induces Pathways Associated with Membrane Biosynthesis in Response to Tissue Damage by Aflatoxin B1.” Toxicology and Applied Pharmacology 282.1 (2015): 52–60.
Version
Author's final manuscript
Abstract
Aflatoxin B[subscript 1] (AFB[subscript 1]) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB[subscript 1]-DNA adducts in AFB[subscript 1]-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB[subscript 1] and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB[subscript 1] administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB[subscript 1]-induced hepatotoxicity. At 24 h after AFB[subscript 1] administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB[subscript 1]-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB[subscript 1] hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1016/j.taap.2014.11.004
