Abstract | BACKGROUND: MATERIALS AND METHODS: In the present study we found that the sensitivity of colon cancer cells to methylation plays a role in its response to alternative therapy involving the green tea polyphenol, epigallocatechin 3-gallate. HDAC and DNMT protein expression were reduced when methylation-sensitive HCT 116 human colon cancer cells was treated with EGCG, but was relatively stable in the HT-29 cell line. This decrease in expression may be partially explained by our finding that DNMT3A and HDAC3 are degraded in the methylation-sensitive colon cancer cells in part by inhibiting their association with the E3 ubiquitin ligase, UHRF1. CONCLUSION: These findings provide a rationale for the development of a targeted therapy for methylation-sensitive colon cancer that can include EGCG in combination with other DNMT and HDAC inhibitors.
|
Authors | Vondina R Moseley, Jay Morris, Rebecca W Knackstedt, Michael J Wargovich |
Journal | Anticancer research
(Anticancer Res)
Vol. 33
Issue 12
Pg. 5325-33
(Dec 2013)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 24324066
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- DNA Primers
- DNMT3A protein, human
- Tea
- Catechin
- epigallocatechin gallate
- DNA (Cytosine-5-)-Methyltransferases
- DNA Methyltransferase 3A
- Histone Deacetylases
- histone deacetylase 3
|
Topics |
- Base Sequence
- Catechin
(analogs & derivatives, pharmacology)
- Colonic Neoplasms
(enzymology, pathology)
- DNA (Cytosine-5-)-Methyltransferases
(genetics, metabolism)
- DNA Methyltransferase 3A
- DNA Primers
- HCT116 Cells
- Histone Deacetylases
(genetics, metabolism)
- Humans
- Proteolysis
- Real-Time Polymerase Chain Reaction
- Tea
(chemistry)
|