Journal
CANCER PREVENTION RESEARCH
Volume 6, Issue 10, Pages 1140-1149Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-13-0216
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Funding
- Kerley-Cade Endowment
- Center for Cancer Prevention and Drug Development at the OUHSC
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Lung cancer is the leading cause of cancer-related deaths. beta-Escin, a triterpene saponin isolated from horse chestnut seeds, was tested for inhibition of lung adenoma and adenocarcinoma induced by the tobacco carcinogen 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice; and its possible mode of action was evaluated using the H460 human lung cancer cell line. At 6 weeks of age, 35 mice were fed AIN-76A-modified diet, and one week later, lung tumors were induced with a single intraperitoneal (i.p.) injection of 10 mu mol NNK/mouse. Three weeks after the NNK treatment, groups of mice were fed either control or experimental diets containing 500 ppm for 20 weeks (10 control, 5 beta-escin) or 36 weeks )15 control, 5 beta-escin) and evaluated for lung tumor via histopathologic methods. Administration of 500 ppm beta-escin significantly suppressed lung tumor (adenoma + adenocarcinoma) formation by more than 40% (P < 0.0015) at 20 weeks and by 53.3% (P < 0.0001) at 37 weeks. beta-Escin inhibited NNK-induced lung adenocarcinoma formation by 65% (P < 0.001 at 20 weeks and by 53% (P < 0.0001) at 37 weeks. Immunohistochemical analysis revealed that lung tumors from mice exposed to beta-escin showed significantly reduced aldehyde dehydrogenase (ALDH)1A1 and phospho-Akt (p-Akt) expression when compared with those in mice fed control diet. Aldefluor assay for ALDH revealed that among H460 lung cancer cells treated with different concentrations of beta-escin (0-40 mu mol/L), the subpopulation of cells with elevated ALDH activity was inhibited significantly. Our findings suggest that b-escin inhibits tobacco carcinogeninduced lung tumor formation by modulating ALDH1A1-positive cells and RhoA/Rock signaling. Cancer Prev Res; 6(10); 1140-9. (C)2013 AACR.
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