Characterization of the biological activity of gamma-glutamyl-Se-methylselenocysteine: a novel, naturally occurring anticancer agent from garlic.
Gamma-glutamyl-Se-methylselenocysteine (GGMSC) has recently been identified as the major Se compound in natural garlic and selenized garlic. Our working hypothesis is that GGMSC serves primarily as a carrier of Se-methylselenocysteine (MSC), which has been demonstrated in past research to be a potent cancer chemopreventive agent in animal carcinogenesis bioassays. The present study was designed to examine the in vivo responses to GGMSC or MSC using a variety of biochemical and biological end points, including (a) urinary Se excretion as a function of bolus dose; (b) tissue Se accumulation profile; (c) anticancer efficacy; and (d) gene expression changes as determined by cDNA array analysis. Our results showed that like MSC, GGMSC was well absorbed p.o., with urinary excretion as the major route for eliminating excess Se. When fed chronically, the profile of Se accumulation in various tissues was very comparable after treatment with either GGMSC or MSC. In rats that had been challenged with a carcinogen, supplementation with either GGMSC or MSC resulted in a lower prevalence of premalignant lesions in the mammary gland, and fewer mammary carcinomas when these early lesions were allowed to progress. More importantly, we found that a short term GGMSC/MSC treatment schedule of 4 weeks immediately after carcinogen dosing was sufficient to provide significant cancer protection, even in the absence of a sustained exposure past the initial 4-week period. With the use of the Clontech Atlas Rat cDNA Array, we further discovered that the gene expression changes induced in mammary epithelial cells of rats that were given either GGMSC or MSC showed a high degree of concordance. On the basis of the collective biology, biochemistry, and molecular biology data, we conclude that GGMSC is an effective anticancer agent with a mechanism of action very similar to that of MSC.
Dong
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Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007408:Intestinal Absorption; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016566:Organoselenium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000493:pharmacokinetics / Q000652:urine; D017279:Selenocysteine / Q000031:analogs & derivatives
D016588:Anticarcinogenic Agents; D016566:Organoselenium Compounds; C424943:glutamyl-Se-methylselenocysteine; D017279:Selenocysteine; D012643:Selenium; D003545:Cysteine; C002979:selenomethylselenocysteine