Chemoprevention of familial adenomatous polyposis development in the APC(min) mouse model by 1,4-phenylene bis (methylene)selenocyanate

Chinthalapally V. Rao, Indranie Cooma, Jose G. Rosa Rodriguez, Barbara Simi, Karam El-Bayoumy, Bandaru S. Reddy

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Epidemiological and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of cancers at several organ sites. We have consistently shown that 1,4-phenylene bis(methylene) selenocyanate (p-XSC) is a highly effective cancer chemopreventive agent against the development of chemically induced cancers in several laboratory animal species. This is the first report describing the preventive effects of p-XSC in an animal model of familial adenomatous polyposis (FAP) containing a germline mutation of the APC gene. Six-week old male (heterozygous) C57BL/6J-APC(min) or wild-type mice were fed high fat diets containing 0, 10 or 20 p.p.m. p-XSC. After 80 days, the mice were killed and their intestines were excised and evaluated for polyps. Multiple samples were also harvested from normal appearing small intestine and colon for molecular analysis. Both the mucosa and polyps from the intestine and colon were assayed for β-catenin, cyclooxygenase (COX)-2 expression and COX isoform activities. Administration of p-XSC in the diet significantly decreased the rate of formation of small intestinal tumors (P < 0.0001) and colon tumors (P < 0.002) in APC(min) mice. p-XSC produced a dose-dependent inhibition of tumors in both small intestine (P < 0.0001) and colon (P < 0.035). Mice fed 20 p.p.m. p-XSC had significantly lower levels of β-catenin expression and COX-2 activity in polyps. These observations demonstrate for the first time that the synthetic organoselenium compound p-XSC possesses antitumor activity against genetically predisposed neoplastic lesions, such as FAP. While the exact mechanism(s) for this antitumor activity of p-XSC remains to be elucidated, it appears that modulation of β-catenin expression and COX-2 activity is associated with inhibition of intestinal polyps.

Original languageEnglish (US)
Pages (from-to)617-621
Number of pages5
JournalCarcinogenesis
Volume21
Issue number4
DOIs
StatePublished - Jan 1 2000

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Adenomatous Polyposis Coli
Chemoprevention
Catenins
Colon
Cyclooxygenase 2
Polyps
Neoplasms
Small Intestine
Intestines
Organoselenium Compounds
Intestinal Polyps
APC Genes
Germ-Line Mutation
Laboratory Animals
High Fat Diet
Prostaglandin-Endoperoxide Synthases
Selenium
Dietary Supplements
1,4-phenylenebis(methylene)selenocyanate
Epidemiologic Studies

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Rao, Chinthalapally V. ; Cooma, Indranie ; Rosa Rodriguez, Jose G. ; Simi, Barbara ; El-Bayoumy, Karam ; Reddy, Bandaru S. / Chemoprevention of familial adenomatous polyposis development in the APC(min) mouse model by 1,4-phenylene bis (methylene)selenocyanate. In: Carcinogenesis. 2000 ; Vol. 21, No. 4. pp. 617-621.
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abstract = "Epidemiological and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of cancers at several organ sites. We have consistently shown that 1,4-phenylene bis(methylene) selenocyanate (p-XSC) is a highly effective cancer chemopreventive agent against the development of chemically induced cancers in several laboratory animal species. This is the first report describing the preventive effects of p-XSC in an animal model of familial adenomatous polyposis (FAP) containing a germline mutation of the APC gene. Six-week old male (heterozygous) C57BL/6J-APC(min) or wild-type mice were fed high fat diets containing 0, 10 or 20 p.p.m. p-XSC. After 80 days, the mice were killed and their intestines were excised and evaluated for polyps. Multiple samples were also harvested from normal appearing small intestine and colon for molecular analysis. Both the mucosa and polyps from the intestine and colon were assayed for β-catenin, cyclooxygenase (COX)-2 expression and COX isoform activities. Administration of p-XSC in the diet significantly decreased the rate of formation of small intestinal tumors (P < 0.0001) and colon tumors (P < 0.002) in APC(min) mice. p-XSC produced a dose-dependent inhibition of tumors in both small intestine (P < 0.0001) and colon (P < 0.035). Mice fed 20 p.p.m. p-XSC had significantly lower levels of β-catenin expression and COX-2 activity in polyps. These observations demonstrate for the first time that the synthetic organoselenium compound p-XSC possesses antitumor activity against genetically predisposed neoplastic lesions, such as FAP. While the exact mechanism(s) for this antitumor activity of p-XSC remains to be elucidated, it appears that modulation of β-catenin expression and COX-2 activity is associated with inhibition of intestinal polyps.",
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Chemoprevention of familial adenomatous polyposis development in the APC(min) mouse model by 1,4-phenylene bis (methylene)selenocyanate. / Rao, Chinthalapally V.; Cooma, Indranie; Rosa Rodriguez, Jose G.; Simi, Barbara; El-Bayoumy, Karam; Reddy, Bandaru S.

In: Carcinogenesis, Vol. 21, No. 4, 01.01.2000, p. 617-621.

Research output: Contribution to journalArticle

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T1 - Chemoprevention of familial adenomatous polyposis development in the APC(min) mouse model by 1,4-phenylene bis (methylene)selenocyanate

AU - Rao, Chinthalapally V.

AU - Cooma, Indranie

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AU - Simi, Barbara

AU - El-Bayoumy, Karam

AU - Reddy, Bandaru S.

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N2 - Epidemiological and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of cancers at several organ sites. We have consistently shown that 1,4-phenylene bis(methylene) selenocyanate (p-XSC) is a highly effective cancer chemopreventive agent against the development of chemically induced cancers in several laboratory animal species. This is the first report describing the preventive effects of p-XSC in an animal model of familial adenomatous polyposis (FAP) containing a germline mutation of the APC gene. Six-week old male (heterozygous) C57BL/6J-APC(min) or wild-type mice were fed high fat diets containing 0, 10 or 20 p.p.m. p-XSC. After 80 days, the mice were killed and their intestines were excised and evaluated for polyps. Multiple samples were also harvested from normal appearing small intestine and colon for molecular analysis. Both the mucosa and polyps from the intestine and colon were assayed for β-catenin, cyclooxygenase (COX)-2 expression and COX isoform activities. Administration of p-XSC in the diet significantly decreased the rate of formation of small intestinal tumors (P < 0.0001) and colon tumors (P < 0.002) in APC(min) mice. p-XSC produced a dose-dependent inhibition of tumors in both small intestine (P < 0.0001) and colon (P < 0.035). Mice fed 20 p.p.m. p-XSC had significantly lower levels of β-catenin expression and COX-2 activity in polyps. These observations demonstrate for the first time that the synthetic organoselenium compound p-XSC possesses antitumor activity against genetically predisposed neoplastic lesions, such as FAP. While the exact mechanism(s) for this antitumor activity of p-XSC remains to be elucidated, it appears that modulation of β-catenin expression and COX-2 activity is associated with inhibition of intestinal polyps.

AB - Epidemiological and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of cancers at several organ sites. We have consistently shown that 1,4-phenylene bis(methylene) selenocyanate (p-XSC) is a highly effective cancer chemopreventive agent against the development of chemically induced cancers in several laboratory animal species. This is the first report describing the preventive effects of p-XSC in an animal model of familial adenomatous polyposis (FAP) containing a germline mutation of the APC gene. Six-week old male (heterozygous) C57BL/6J-APC(min) or wild-type mice were fed high fat diets containing 0, 10 or 20 p.p.m. p-XSC. After 80 days, the mice were killed and their intestines were excised and evaluated for polyps. Multiple samples were also harvested from normal appearing small intestine and colon for molecular analysis. Both the mucosa and polyps from the intestine and colon were assayed for β-catenin, cyclooxygenase (COX)-2 expression and COX isoform activities. Administration of p-XSC in the diet significantly decreased the rate of formation of small intestinal tumors (P < 0.0001) and colon tumors (P < 0.002) in APC(min) mice. p-XSC produced a dose-dependent inhibition of tumors in both small intestine (P < 0.0001) and colon (P < 0.035). Mice fed 20 p.p.m. p-XSC had significantly lower levels of β-catenin expression and COX-2 activity in polyps. These observations demonstrate for the first time that the synthetic organoselenium compound p-XSC possesses antitumor activity against genetically predisposed neoplastic lesions, such as FAP. While the exact mechanism(s) for this antitumor activity of p-XSC remains to be elucidated, it appears that modulation of β-catenin expression and COX-2 activity is associated with inhibition of intestinal polyps.

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