Limits...
Genistein affects histone modifications on Dickkopf-related protein 1 (DKK1) gene in SW480 human colon cancer cell line.

Wang H, Li Q, Chen H - PLoS ONE (2012)

Bottom Line: This indicates that increased histone acetylation is associated with the genistein-induced DKK1 expression.In conclusion, genistein treatment decreases cell growth and proliferation in colon cancer cell lines.The effect is associated with the increased DKK1 expression through the induction of histone acetylation at the DKK1 promoter region.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

ABSTRACT
Genistein (GEN) is a plant-derived isoflavone and can block uncontrolled cell growth in colon cancer by inhibiting the WNT signaling pathway. This study aimed to test the hypothesis that the enhanced gene expression of the WNT signaling pathway antagonist, DKK1 by genistein treatment is associated with epigenetic modifications of the gene in colon cancer cells. Genistein treatment induced a concentration-dependent G2 phase arrest in the human colon cancer cell line SW480 and reduced cell proliferation. Results from several other human colon cancer cell lines confirmed the growth inhibitory effects of genistein. Overexpression of DKK1 confirmed its involvement in growth inhibition. Knockdown of DKK1 expression by siRNA slightly induced cell growth. DKK1 gene expression was increased by genistein in SW480 and HCT15 cells. DNA methylation at the DKK1 promoter was not affected by genistein treatment in all the cell lines tested. On the other hand, genistein induced histone H3 acetylation of the DKK1 promoter region in SW480 and HCT15 cells. This indicates that increased histone acetylation is associated with the genistein-induced DKK1 expression. The association between histone acetylation and DKK1 gene expression is confirmed by the histone deacetylase inhibitor trichostatin A (TSA) treatment. In conclusion, genistein treatment decreases cell growth and proliferation in colon cancer cell lines. The effect is associated with the increased DKK1 expression through the induction of histone acetylation at the DKK1 promoter region.

Show MeSH

Related in: MedlinePlus

DKK1 mRNA expression after TSA treatment.DKK1 mRNA level was analyzed in SW480 cells treated with 50, 100 or 200 nmol/L of TSA (TSA50, TSA100, and TSA200, respectively) for 1 d. Genistein treatment was done as previously described. mRNA expression level was analyzed using RT-PCR. Three independent cell samples were analyzed and presented as the mean±SEM. Values with different letters differ (p<0.05).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3399800&req=5

pone-0040955-g007: DKK1 mRNA expression after TSA treatment.DKK1 mRNA level was analyzed in SW480 cells treated with 50, 100 or 200 nmol/L of TSA (TSA50, TSA100, and TSA200, respectively) for 1 d. Genistein treatment was done as previously described. mRNA expression level was analyzed using RT-PCR. Three independent cell samples were analyzed and presented as the mean±SEM. Values with different letters differ (p<0.05).

Mentions: TSA is a histone deacetylase (HDAC) inhibitor that interacts with most of the HDAC family members and induces acetylation of histones. To confirm the effects of genistein-induced histone acetylation on DKK1 transcription, we treated SW480 cells with a series of TSA concentrations and compared the results to genistein treatment. The mRNA expression of DKK1 was increased significantly by the TSA treatment in a dose-dependent manner, similar to the result observed from genistein treatment (p<0.05, Fig. 7).


Genistein affects histone modifications on Dickkopf-related protein 1 (DKK1) gene in SW480 human colon cancer cell line.

Wang H, Li Q, Chen H - PLoS ONE (2012)

DKK1 mRNA expression after TSA treatment.DKK1 mRNA level was analyzed in SW480 cells treated with 50, 100 or 200 nmol/L of TSA (TSA50, TSA100, and TSA200, respectively) for 1 d. Genistein treatment was done as previously described. mRNA expression level was analyzed using RT-PCR. Three independent cell samples were analyzed and presented as the mean±SEM. Values with different letters differ (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3399800&req=5

pone-0040955-g007: DKK1 mRNA expression after TSA treatment.DKK1 mRNA level was analyzed in SW480 cells treated with 50, 100 or 200 nmol/L of TSA (TSA50, TSA100, and TSA200, respectively) for 1 d. Genistein treatment was done as previously described. mRNA expression level was analyzed using RT-PCR. Three independent cell samples were analyzed and presented as the mean±SEM. Values with different letters differ (p<0.05).
Mentions: TSA is a histone deacetylase (HDAC) inhibitor that interacts with most of the HDAC family members and induces acetylation of histones. To confirm the effects of genistein-induced histone acetylation on DKK1 transcription, we treated SW480 cells with a series of TSA concentrations and compared the results to genistein treatment. The mRNA expression of DKK1 was increased significantly by the TSA treatment in a dose-dependent manner, similar to the result observed from genistein treatment (p<0.05, Fig. 7).

Bottom Line: This indicates that increased histone acetylation is associated with the genistein-induced DKK1 expression.In conclusion, genistein treatment decreases cell growth and proliferation in colon cancer cell lines.The effect is associated with the increased DKK1 expression through the induction of histone acetylation at the DKK1 promoter region.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

ABSTRACT
Genistein (GEN) is a plant-derived isoflavone and can block uncontrolled cell growth in colon cancer by inhibiting the WNT signaling pathway. This study aimed to test the hypothesis that the enhanced gene expression of the WNT signaling pathway antagonist, DKK1 by genistein treatment is associated with epigenetic modifications of the gene in colon cancer cells. Genistein treatment induced a concentration-dependent G2 phase arrest in the human colon cancer cell line SW480 and reduced cell proliferation. Results from several other human colon cancer cell lines confirmed the growth inhibitory effects of genistein. Overexpression of DKK1 confirmed its involvement in growth inhibition. Knockdown of DKK1 expression by siRNA slightly induced cell growth. DKK1 gene expression was increased by genistein in SW480 and HCT15 cells. DNA methylation at the DKK1 promoter was not affected by genistein treatment in all the cell lines tested. On the other hand, genistein induced histone H3 acetylation of the DKK1 promoter region in SW480 and HCT15 cells. This indicates that increased histone acetylation is associated with the genistein-induced DKK1 expression. The association between histone acetylation and DKK1 gene expression is confirmed by the histone deacetylase inhibitor trichostatin A (TSA) treatment. In conclusion, genistein treatment decreases cell growth and proliferation in colon cancer cell lines. The effect is associated with the increased DKK1 expression through the induction of histone acetylation at the DKK1 promoter region.

Show MeSH
Related in: MedlinePlus