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KMID : 1007520080170051079
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Food Science and Biotechnology
2008 Volume.17 No. 5 p.1079 ~ p.1085
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Up-regulation of Aldo-keto Reductase 1C3 Expression in Sulforaphane-treated MCF-7 Breast Cancer Cells
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Lee Sang-Han
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Abstract
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The chemopreventive activity of sulforaphane (SFN) occurs through its inhibition of carcinogen-activating enzymes and its induction of detoxification enzymes. However, the exact mechanisms by which SFN exerts its anti-carcinogenic effects are not fully understood. Therefore, the mechanisms underlying the cytoprotective effects of SFN were examined in MCF-7
breast cancer cells. Exposure of cells to SFN (10 μM) induced a transcriptional change in the AKR1C3 gene, which is one of aldo-keto reductases (AKRs) family that is associated with detoxification and antioxidant response. Further analysis revealed that SFN elicited a dose- and time-dependent increase in the expression of both the NRF2 and AKR1C3 proteins. Moreover, this up-regulation of AKR1C3 was inhibited by pretreatment with antioxidant, N-acetyl-L-cysteine (NAC), which suggests that the up-regulation of AKR1C3 expression induced by SFN involves reactive oxygen species (ROS) signaling. Furthermore, pretreatment of cells with LY294002, a pharmacologic inhibitor of phosphatidylinositol 3-kinase (PI3K), suppressed the SFNaugmented Nrf2 activation and AKR1C3 expression; however, inhibition of PKC or MEK1/2 signaling with Go6976 or PD98059, respectively, did not alter SFN-induced AKR1C3 expression. Collectively, these data suggest that SFN can modulate the expression of the AKR1C3 in MCF-7 cells by activation of PI3K via the generation of ROS.
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KEYWORD
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sulforaphane, AKR1C3, cytoprotection, phosphatidylinositol 3-kinase, reactive oxygen species
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