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
02/02/2013Pubmed ID
23368921Pubmed Central ID
PMC3570951DOI
10.1080/01635581.2013.741759Scopus ID
2-s2.0-84873705144 (requires institutional sign-in at Scopus site) 120 CitationsAbstract
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 YWMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnthocyanins
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
