The mechanism of action of the anticancer effects of selenomethionine on colon cancer

Persistent Link:
http://hdl.handle.net/10150/290479
Title:
The mechanism of action of the anticancer effects of selenomethionine on colon cancer
Author:
Baines, Antonio Thomas
Issue Date:
2001
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Selenomethionine, an organic derivative of selenium, has been found to be the predominate selenium component of the dietary cancer chemopreventive agent selenized yeast that has been shown to decrease the incidence and mortality rate of lung, colon, and prostate cancers. Another organic selenium derivative found in the selenized yeast is Se-methylselenocysteine. However, the mechanism of action of the anti-cancer effects of these selenium compounds has yet to be identified. To evaluate the effects of these compounds on growth of the cancer cell types mentioned earlier, various cancer cell lines were treated with either compound. Both selenium compounds were able to induce growth inhibition and alterations in the cell cycle, with selenomethionine being the most potent. Previously, our laboratory has shown that treating cancer cells with selenomethionine depleted polyamines. Polyamines are cations that are needed for various roles in growth and proliferation. To extend these findings to an in vivo model, we gave selenomethionine in the diet (1ppm and 2ppm) for 16 weeks to male F344 rats in the azoxymethane (AOM) rat colon carcinogenesis model. The results showed no significant changes in colonic polyamine levels, however, there were significant changes in the development of microadenomas between control and treated groups. Selenomethionine was able to decrease the promotional effects of colon carcinogenesis through a polyamine-independent mechanism. Next, we tested the hypothesis that selenomethionine might affect cell growth by mechanisms involving cyclooxygenases, specifically the inducible isoform COX-2. Cyclooxygenases (COX-1 and COX-2) are enzymes that metabolize arachidonic acid to various prostaglandins. The human adenocarcinoma cell lines HT-29 and HCA-7, that express variable levels of COX-2, were treated for up to 6 days with selenomethionine. Selenomethionine induced growth inhibition in both cell lines and decreased COX-2 protein expression in the treated groups. Also, prostaglandin (PG) E2 levels were decreased in both treated groups at the latter timepoints. The HCA-7 cell line had a dose and time-dependent decrease in RNA levels treated with selenomethionine, whereas, no effects were observed on RNA expression of the HT-29 cell line. In summary, selenomethionine has chemopreventive effects in colon carcinogenesis by potentially modulating COX-2 proteins in cancer cells.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Psychology, Physiological.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Pharmacology and Toxicology
Degree Grantor:
University of Arizona
Advisor:
Nelson, Mark A.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleThe mechanism of action of the anticancer effects of selenomethionine on colon canceren_US
dc.creatorBaines, Antonio Thomasen_US
dc.contributor.authorBaines, Antonio Thomasen_US
dc.date.issued2001en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractSelenomethionine, an organic derivative of selenium, has been found to be the predominate selenium component of the dietary cancer chemopreventive agent selenized yeast that has been shown to decrease the incidence and mortality rate of lung, colon, and prostate cancers. Another organic selenium derivative found in the selenized yeast is Se-methylselenocysteine. However, the mechanism of action of the anti-cancer effects of these selenium compounds has yet to be identified. To evaluate the effects of these compounds on growth of the cancer cell types mentioned earlier, various cancer cell lines were treated with either compound. Both selenium compounds were able to induce growth inhibition and alterations in the cell cycle, with selenomethionine being the most potent. Previously, our laboratory has shown that treating cancer cells with selenomethionine depleted polyamines. Polyamines are cations that are needed for various roles in growth and proliferation. To extend these findings to an in vivo model, we gave selenomethionine in the diet (1ppm and 2ppm) for 16 weeks to male F344 rats in the azoxymethane (AOM) rat colon carcinogenesis model. The results showed no significant changes in colonic polyamine levels, however, there were significant changes in the development of microadenomas between control and treated groups. Selenomethionine was able to decrease the promotional effects of colon carcinogenesis through a polyamine-independent mechanism. Next, we tested the hypothesis that selenomethionine might affect cell growth by mechanisms involving cyclooxygenases, specifically the inducible isoform COX-2. Cyclooxygenases (COX-1 and COX-2) are enzymes that metabolize arachidonic acid to various prostaglandins. The human adenocarcinoma cell lines HT-29 and HCA-7, that express variable levels of COX-2, were treated for up to 6 days with selenomethionine. Selenomethionine induced growth inhibition in both cell lines and decreased COX-2 protein expression in the treated groups. Also, prostaglandin (PG) E2 levels were decreased in both treated groups at the latter timepoints. The HCA-7 cell line had a dose and time-dependent decrease in RNA levels treated with selenomethionine, whereas, no effects were observed on RNA expression of the HT-29 cell line. In summary, selenomethionine has chemopreventive effects in colon carcinogenesis by potentially modulating COX-2 proteins in cancer cells.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectPsychology, Physiological.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorNelson, Mark A.en_US
dc.identifier.proquest3023494en_US
dc.identifier.bibrecord.b41957519en_US
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