Chemopreventive Effects of the p53-Modulating Agents CP-31398 and Prima-1 in Tobacco Carcinogen-Induced Lung Tumorigenesis in A/J Mice
| Autor: | Jagan M.R. Patlolla, Misty Brewer, Li Qian, Dhimant Desai, Yuting Zhang, Chinthalapally V. Rao, Altaf Mohammed, Shantu Amin, Levy Kopelovich, Stan Lightfoot |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Lung Adenoma business.industry medicine.medical_treatment Intraperitoneal injection Cancer medicine.disease medicine.disease_cause lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens lcsh:RC254-282 medicine.anatomical_structure Apoptosis medicine Cancer research Adenocarcinoma Lung cancer Carcinogenesis business |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 15, Iss 9, Pp 1018-1027 (2013) |
| ISSN: | 1476-5586 |
| DOI: | 10.1593/neo.131256 |
| Popis: | Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse) by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group) or 34 weeks (15 mice/group) to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001) lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001) lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation. |
| Databáze: | OpenAIRE |
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