Carcinogenesis, Vol 19, 597-604, Copyright © 1998 by Oxford University Press
ES Fiala, ME Staretz, GA Pandya, K El-Bayoumy and SR Hamilton
The organoselenium compounds benzyl selenocyanate (BSC) and 1,4-
phenylenebis(methylene)selenocyanate (p-XSC), as well as sodium selenite,
are effective chemopreventive agents for various chemically induced tumors
in animal models at both the initiation and postinitiation stages. The
mechanisms involved at the postinitiation stage are not clear. Because
several lines of evidence indicate that inhibition of excess DNA
(cytosine-5)-methyltransferase (Mtase) may be a sufficient factor for the
suppression or reversion of carcinogenesis, we examined the effects of
sodium selenite, BSC, p-XSC and benzyl thiocyanate (BTC), the sulfur analog
of BSC, on Mtase activity in nuclear extracts of human colon carcinomas,
and of p-XSC on the Mtase activity of HCT116 human colon carcinoma cells in
culture. For this purpose, we developed an improved Mtase assay, in which
the incorporation of the methyl-[3H] group from S-adenosyl[methyl-
3H]methionine into deoxycytidine of poly(dI-dC)-poly(dI-dC), is
specifically determined by HPLC with radioflow detection after enzymatic
hydrolysis, enhancing specificity and reliability. In a variation, using
SssI methyltransferase and labeled S- adenosylmethionine, the overall
methylation status of DNA in various tissues can also be compared.
Selenite, BSC and p-XSC inhibited Mtase extracted from a human colon
carcinoma with IC50s of 3.8, 8.1 and 5.2 microM, respectively; BTC had no
effect. p-XSC also inhibited the Mtase activity and growth of human colon
carcinoma HCT116 cells, with an IC50 of approximately 20 microM. The
improved Mtase assay should prove to be a reliable method for screening
potential Mtase inhibitors, especially using cells in culture. We suggest
that inhibition of Mtase may be a major mechanism of chemoprevention by
selenium compounds at the postinitiation stage of carcinogenesis.
ARTICLES
Inhibition of DNA cytosine methyltransferase by chemopreventive selenium compounds, determined by an improved assay for DNA cytosine methyltransferase and DNA cytosine methylation
Division of Biochemical Pharmacology, American Health Foundation, Valhalla, NY 10595, USA. fiala@idt.net
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Wu, G. H. Lyons, R. D. Graham, and M. F. Fenech The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay Mutagenesis, May 1, 2009; 24(3): 225 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Xiang, R. Zhao, G. Song, and W. Zhong Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells Carcinogenesis, November 1, 2008; 29(11): 2175 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kopelovich, J. R. Fay, C. C. Sigman, and J. A. Crowell The Mammalian Target of Rapamycin Pathway as a Potential Target for Cancer Chemoprevention Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1330 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S Perry, R. Foley, K. Woodson, and M. Lawler The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 357 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stresemann, B. Brueckner, T. Musch, H. Stopper, and F. Lyko Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res., March 1, 2006; 66(5): 2794 - 2800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lyko and R. Brown DNA Methyltransferase Inhibitors and the Development of Epigenetic Cancer Therapies J Natl Cancer Inst, October 19, 2005; 97(20): 1498 - 1506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Belinsky Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer Carcinogenesis, September 1, 2005; 26(9): 1481 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Duffield-Lillico, I. Shureiqi, and S. M. Lippman Can Selenium Prevent Colorectal Cancer? A Signpost From Epidemiology J Natl Cancer Inst, November 17, 2004; 96(22): 1645 - 1647. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cao, F. A. Durrani, and Y. M. Rustum Selective Modulation of the Therapeutic Efficacy of Anticancer Drugs by Selenium Containing Compounds against Human Tumor Xenografts Clin. Cancer Res., April 1, 2004; 10(7): 2561 - 2569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopelovich, J. A. Crowell, and J. R. Fay The Epigenome as a Target for Cancer Chemoprevention J Natl Cancer Inst, December 3, 2003; 95(23): 1747 - 1757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Belinsky, D. M. Klinge, C. A. Stidley, J.-P. Issa, J. G. Herman, T. H. March, and S. B. Baylin Inhibition of DNA Methylation and Histone Deacetylation Prevents Murine Lung Cancer Cancer Res., November 1, 2003; 63(21): 7089 - 7093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Lee, Y.-C. Tang, Y.-H. Chen, C.-M. Wong, and A.-P. Tsou Selenite-induced Survival of HuH7 Hepatoma Cells Involves Activation of Focal Adhesion Kinase-Phosphatidylinositol 3-Kinase-Akt Pathway and Rac1 J. Biol. Chem., October 10, 2003; 278(41): 39615 - 39624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Davis and E. O. Uthus Dietary Folate and Selenium Affect Dimethylhydrazine-Induced Aberrant Crypt Formation, Global DNA Methylation and One-Carbon Metabolism in Rats J. Nutr., September 1, 2003; 133(9): 2907 - 2914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Reid, A. J. Duffield-Lillico, L. Garland, B. W. Turnbull, L. C. Clark, and J. R. Marshall Selenium Supplementation and Lung Cancer Incidence: An Update of the Nutritional Prevention of Cancer Trial Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1285 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. R. Seo, M. R. Kelley, and M. L. Smith From the Cover: Selenomethionine regulation of p53 by a ref1-dependent redox mechanism PNAS, October 29, 2002; 99(22): 14548 - 14553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Belinsky, W. A. Palmisano, F. D. Gilliland, L. A. Crooks, K. K. Divine, S. A. Winters, M. J. Grimes, H. J. Harms, C. S. Tellez, T. M. Smith, et al. Aberrant Promoter Methylation in Bronchial Epithelium and Sputum from Current and Former Smokers Cancer Res., April 1, 2002; 62(8): 2370 - 2377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Davis and E. O. Uthus Dietary Selenite and Azadeoxycytidine Treatments Affect Dimethylhydrazine-Induced Aberrant Crypt Formation in Rat Colon and DNA Methylation in HT-29 Cells J. Nutr., February 1, 2002; 132(2): 292 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin, K. Asgari, M. J. Putzi, W. R. Gage, X. Yu, B. S. Cornblatt, A. Kumar, S. Piantadosi, T. L. DeWeese, A. M. De Marzo, et al. Reversal of GSTP1 CpG Island Hypermethylation and Reactivation of {pi}-Class Glutathione S-Transferase (GSTP1) Expression in Human Prostate Cancer Cells by Treatment with Procainamide Cancer Res., December 1, 2001; 61(24): 8611 - 8616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kim, U. Jung, D.-Y. Cho, and A.-S. Chung Se-Methylselenocysteine induces apoptosis through caspase activation in HL-60 cells Carcinogenesis, April 1, 2001; 22(4): 559 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Woodson, J. Mason, S.-W. Choi, T. Hartman, J. Tangrea, J. Virtamo, P. R. Taylor, and D. Albanes Hypomethylation of p53 in Peripheral Blood DNA Is Associated with the Development of Lung Cancer Cancer Epidemiol. Biomarkers Prev., January 1, 2001; 10(1): 69 - 74. [Abstract] [Full Text]
|
|
|
|
|
|
K. Ghoshal, S. Majumder, Z. Li, X. Dong, and S. T. Jacob Suppression of Metallothionein Gene Expression in a Rat Hepatoma Because of Promoter-specific DNA Methylation J. Biol. Chem., January 7, 2000; 275(1): 539 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minamoto, M. Mai, and Z.'e. Ronai Environmental factors as regulators and effectors of multistep carcinogenesis Carcinogenesis, April 1, 1999; 20(4): 519 - 527. [Abstract] [Full Text] [PDF]
|
|