Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid and atorvastatin
Pereira, MA; Warner, BM; Knobloch, TJ; Weghorst, CM; Lubet, RA; Steele, VE; Casto, BC
HERO ID
1455067
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 1455067 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid and atorvastatin |
| Authors | Pereira, MA; Warner, BM; Knobloch, TJ; Weghorst, CM; Lubet, RA; Steele, VE; Casto, BC |
| Journal | International Journal of Cancer |
| Volume | 131 |
| Issue | 6 |
| Page Numbers | 1277-1286 |
| Abstract | Atorvastatin and suberoylanilide hydroxamic acid (SAHA) were evaluated for chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 mg/kg atorvastatin, and combinations containing SAHA and atorvastatin administered in their diet. SAHA and both combinations, but not atorvastatin, decreased the multiplicity of lung tumors, including large adenomas and adenocarcinomas with the combinations demonstrating the greatest efficacy. In Experiment 2, lung tumors were induced by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol in strain A/J mice followed by 180 mg/kg atorvastatin, 500 mg/kg SAHA, or both drugs administered in the diet. SAHA and the combination of both drugs, but not atorvastatin alone, decreased the multiplicity of lung tumors and large tumors, with the combination demonstrating greater efficacy. In Experiment 3, lung tumors were induced by 1,2-dimethylhydrazine in Swiss-Webster mice followed by 160 mg/kg atorvastatin, 400 mg/kg SAHA, or a combination of both drugs administered in the diet. SAHA and the combination, but not atorvastatin, decreased the multiplicity of lung tumors with the combination demonstrating greater efficacy. The multiplicity of colon tumors was decreased by SAHA, atorvastatin, and the combination, without any significant difference in their efficacy. mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways. Atorvastatin demonstrated chemoprevention activity as indicated by the enhancement of the efficacy of SAHA to prevent mouse lung tumors. |
| Doi | 10.1002/ijc.27395 |
| Pmid | 22161747 |
| Wosid | WOS:000306735700027 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000306735700027Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864151714&doi=10.1002%2fijc.27395&partnerID=40&md5=ffd53618cdbd9b1ece350c3419180b45 |
| Is Public | Yes |
| Language Text | English |
| Keyword | co-chemoprevention; mouse lung tumors; combinations; suberoylanilide hydroxamic acid; atorvastatin |