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Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells. Nutr Cancer 2013;65(1):118-25

Date

02/02/2013

Pubmed ID

23368921

Pubmed Central ID

PMC3570951

DOI

10.1080/01635581.2013.741759

Scopus ID

2-s2.0-84873705144   71 Citations

Abstract

We previously reported that oral administration of black raspberry powder decreased promoter methylation of tumor suppressor genes in tumors from patients with colorectal cancer. The anthocyanins (ACs) in black raspberries are responsible, at least in part, for their cancer-inhibitory effects. In the present study, we asked if ACs are responsible for the demethylation effects observed in colorectal cancers. Three days of treatment of ACs at 0.5, 5, and 25 μg/ml suppressed activity and protein expression of DNMT1 and DNMT3B in HCT116, Caco2 and SW480 cells. Promoters of CDKN2A, and SFRP2, SFRP5, and WIF1, upstream of Wnt pathway, were demethylated by ACs. mRNA expression of some of these genes was increased. mRNA expression of β-catenin and c-Myc, downstream of Wnt pathway, and cell proliferation were decreased; apoptosis was increased. ACs were taken up into HCT116 cells and were differentially localized with DNMT1 and DNMT3B in the same cells visualized using confocal laser scanning microscopy. Although it was reported that DNMT3B is regulated by c-Myc in mouse lymphoma, DNMT3B did not bind with c-Myc in HCT116 cells. In conclusion, our results suggest that ACs are responsible, at least in part, for the demethylation effects of whole black raspberries in colorectal cancers.

Author List

Wang LS, Kuo CT, Cho SJ, Seguin C, Siddiqui J, Stoner K, Weng YI, Huang TH, Tichelaar J, Yearsley M, Stoner GD, Huang YW

Authors

Yi-Wen Huang PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Li-Shu Wang PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Anthocyanins
Caco-2 Cells
Cell Line, Tumor
Colonic Neoplasms
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
DNA Methylation
Enzyme Inhibitors
Eye Proteins
Genes, Tumor Suppressor
Genes, p16
Humans
Membrane Proteins
Promoter Regions, Genetic
Repressor Proteins
Rosaceae
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1