Abstract 194: Delay in the progression of lung adenoma to adenocarcinoma in mice by oral consumption of pomegranate fruit extract.

Lung cancer has the highest United States and worldwide rate of cancer mortality, exceeding the mortality rates of colorectal, breast and prostate cancers combined. Tobacco smoking is well established as the major etiological risk factor for lung cancer, contributing to an increased risk in long-term smokers compared with non-smokers. The risk of the development of lung cancer in lifelong smokers is 20-40 times higher than that in non-smokers. Moreover, tobacco use accounts for 30% of overall lung cancer mortality. Given the large population at increased risk of developing lung cancer, the development of approaches to prevent smoking related lung cancer would have great clinical benefit. Pomegranate (Punica granatum, Punicaceae), is an edible fruit cultivated in Mediterranean countries, Afghanistan, India, China, Japan, Russia and the United States. Based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, pomegranate fruit extract (PFE) was found to contain anthocyanins (such as delphinidin, cyanidin and pelargonidin) and several hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose) which account for 92% of the antioxidant activity of the whole fruit. We have earlier reported that PFE inhibits prosurvival signaling pathways in human lung carcinoma A549 cells and tumor growth in athymic nude mice (Carcinogenesis 2007; 28:163-73) and A/J mice (Cancer Res 2007; 67:3475-82). In this study, the effect of PFE consumption during progression of lung adenomas to adenocarcinomas was investigated in two mouse tumor protocols. NNK, a tobacco-specific N-nitrosamine, is believed to be one of the most promising candidates of lung carcinogen in humans. B(a)P is one of the most ubiquitous environmental polycyclic aromatic hydrocarbons present in automobile exhaust and cigarette smoke and it induces lung tumors in mice. Since majority of current and ex-smokers have small nodules, it is highly desirable to prevent additional growth of lung cancer after the appearance of nodules. To mimic this situation, PFE (0.2% PFE, w/v) was given to A/J mice in drinking water after the establishment of lung adenomas induced by NNK and B(a)P. Treatment with PFE significantly reduced the lung tumor multiplicity by 33% in mice treated with NNK and 29% in B(a)P-treated mice. PFE also caused significant reduction in the expression of COX-2, RAR-β, VEGF, CD-31 and angiopoietin-2 in lungs of mice treated with NNK and B(a)P. On administration of PFE, there was decrease in the multiplicity and incidence of lung adenomas and adenocarcinomas in mice treated with NNK and B(a)P. Thus, our results indicate that PFE has the potential to be developed as an agent against tobacco smoke-induced lung cancer and for improving the quality of life of early stage lung cancer patients and ex-smokers. Citation Format: Naghma Khan, Ruth Sullivan, Tien Hoang, Tejaswi Dittakavi, Hasan Mukhtar. Delay in the progression of lung adenoma to adenocarcinoma in mice by oral consumption of pomegranate fruit extract. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 194. doi:10.1158/1538-7445.AM2013-194