Reference Detail

Ref Type

Journal Article

PMID

(22161747)

Authors

Pereira MA, Warner BM, Knobloch TJ, Weghorst CM, Lubet RA, Steele VE, Casto BC

Title

Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid and atorvastatin.

Journal	Vol	Issue	Date	Pages	Journal Short Title
International journal of cancer. Journal international du cancer	131	6	2012 Sep 15	1277-86	Int J Cancer

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References