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Effects of co-treatment with sulforaphane and autophagy modulators on uridine 5'-diphospho-glucuronosyltransferase 1A isoforms and cytochrome P450 3A4 expression in Caco-2 human colon cancer cells.

Wang M, Zhu JY, Chen S, Qing Y, Wu D, Lin YM, Luo JZ, Han W, Li YQ - Oncol Lett (2014)

Bottom Line: Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy.The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction.These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics and Gastroenterology, Qi-Lu Hospital of Shandong University, Key Laboratory of Proteomics of Shandong, Jinan, Shandong 250012, P.R. China.

ABSTRACT
Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy. Uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT)1A induction is one of the mechanisms that is responsible for the cancer chemopreventive activity of SFN. The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction. These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer.

No MeSH data available.


Related in: MedlinePlus

Induction of Nrf2 nuclear translocation in Caco-2 cells was examined by immunocytochemistry. Cells were treated for 24 h with 25 μM SFN, 10 nM rapamycin, or a combination of the two. Images are representative of three independent experiments (magnification, ×630). Nrf2, nuclear factor erythroid 2-related factor 2; SFN, sulforaphane.
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f6-ol-08-06-2407: Induction of Nrf2 nuclear translocation in Caco-2 cells was examined by immunocytochemistry. Cells were treated for 24 h with 25 μM SFN, 10 nM rapamycin, or a combination of the two. Images are representative of three independent experiments (magnification, ×630). Nrf2, nuclear factor erythroid 2-related factor 2; SFN, sulforaphane.

Mentions: Under basal conditions, Nrf2 is sequestered in the cytoplasm by Keap1 and, therefore, is not involved in the induction of phase II enzymes. The interaction between Nrf2 and Keap1 is perturbed in response to chemical or oxidative stress, resulting in the translocation of Nrf2 into the nucleus (20). Nrf2 may then bind to the AREs to stimulate the transcription of phase II enzymes, including UGT1A isoforms (21). Therefore, in the present study, Nrf2 localization to the cytoplasm and nucleus of Caco-2 cells was monitored by immunocytochemistry. As presented in Fig. 6, a small quantity of Nrf2 protein (indicated by green fluorescence) was restricted to the cytoplasm in the DMSO-treated control. Treatment with SFN alone caused the accumulation of Nrf2 in the nuclear region, with SFN/rapamycin combination treatment resulting in elevated Nrf2 protein staining, particularly increased Nrf2 nuclear staining. This indicated that the transcription factor, Nrf2 may be significant in the induction of UGT1A1, UGT1A8 and UGT1A10 expression. Caco-2 cells that were treated with rapamycin alone (data not shown) exhibited similar results to the DMSO-treated control, as Nrf2 only exhibited a marginal quantity of cytosolic fluorescence.


Effects of co-treatment with sulforaphane and autophagy modulators on uridine 5'-diphospho-glucuronosyltransferase 1A isoforms and cytochrome P450 3A4 expression in Caco-2 human colon cancer cells.

Wang M, Zhu JY, Chen S, Qing Y, Wu D, Lin YM, Luo JZ, Han W, Li YQ - Oncol Lett (2014)

Induction of Nrf2 nuclear translocation in Caco-2 cells was examined by immunocytochemistry. Cells were treated for 24 h with 25 μM SFN, 10 nM rapamycin, or a combination of the two. Images are representative of three independent experiments (magnification, ×630). Nrf2, nuclear factor erythroid 2-related factor 2; SFN, sulforaphane.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214451&req=5

f6-ol-08-06-2407: Induction of Nrf2 nuclear translocation in Caco-2 cells was examined by immunocytochemistry. Cells were treated for 24 h with 25 μM SFN, 10 nM rapamycin, or a combination of the two. Images are representative of three independent experiments (magnification, ×630). Nrf2, nuclear factor erythroid 2-related factor 2; SFN, sulforaphane.
Mentions: Under basal conditions, Nrf2 is sequestered in the cytoplasm by Keap1 and, therefore, is not involved in the induction of phase II enzymes. The interaction between Nrf2 and Keap1 is perturbed in response to chemical or oxidative stress, resulting in the translocation of Nrf2 into the nucleus (20). Nrf2 may then bind to the AREs to stimulate the transcription of phase II enzymes, including UGT1A isoforms (21). Therefore, in the present study, Nrf2 localization to the cytoplasm and nucleus of Caco-2 cells was monitored by immunocytochemistry. As presented in Fig. 6, a small quantity of Nrf2 protein (indicated by green fluorescence) was restricted to the cytoplasm in the DMSO-treated control. Treatment with SFN alone caused the accumulation of Nrf2 in the nuclear region, with SFN/rapamycin combination treatment resulting in elevated Nrf2 protein staining, particularly increased Nrf2 nuclear staining. This indicated that the transcription factor, Nrf2 may be significant in the induction of UGT1A1, UGT1A8 and UGT1A10 expression. Caco-2 cells that were treated with rapamycin alone (data not shown) exhibited similar results to the DMSO-treated control, as Nrf2 only exhibited a marginal quantity of cytosolic fluorescence.

Bottom Line: Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy.The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction.These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics and Gastroenterology, Qi-Lu Hospital of Shandong University, Key Laboratory of Proteomics of Shandong, Jinan, Shandong 250012, P.R. China.

ABSTRACT
Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy. Uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT)1A induction is one of the mechanisms that is responsible for the cancer chemopreventive activity of SFN. The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction. These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer.

No MeSH data available.


Related in: MedlinePlus