Abstract 951: Inhibition of lung tumorigenesis by oral consumption of pomegranate fruit extract

Abstract

Abstract Lung cancer is the most common cause of cancer mortality worldwide and continues to be a major health problem, exceeding the combined mortality rates of colorectal, breast and prostate cancers. It has proven difficult to control lung cancer with conventional therapeutic and surgical approaches, and generally the prognosis is poor with an overall five-year survival rate of 10-14% in the USA. A competent approach to reduce the mortality from lung cancer is the early detection of premalignant lesions as the survival of early stage lung cancer patients is much better as compared to patients with advanced cancers. The current mainstays of lung cancer therapy are surgical resection, radiation ablation and systemic chemotherapy with considerable toxicity. However, it appears unlikely that these therapies can cause striking improvements in near future. Thus, effective approaches to the prevention of lung cancer need to be developed, especially efforts targeted to the progression of preneoplastic and benign neoplastic lesions to more malignant lung tumors. The pomegranate (Punica granatum; Punicaceae) fruit has been used for centuries in ancient cultures for its medicinal purposes and we have been defining the chemopreventive effects of pomegranate fruit extract (PFE). Based on MALDI-TOF MS analysis, PFE was found to contain anthocyanins (such as delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose). We have earlier shown 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 chemopreventive activity of PFE during progression of lung adenomas was investigated in two mouse tumor protocols. Female A/J mice were treated with 0.2% PFE in drinking water (w/v, equivalent of human consumption of juice derived from two fruits) till the termination of the experiment. One week after treatment with PFE, mice were given a single i.p. injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at dose of 100 mg/kg body weight or urethane at dose of 1 mg/g body weight. Mice were sacrificed at 16 weeks after NNK treatment and 20 weeks after treated with urethane. PFE administration significantly reduced the lung tumor multiplicity by 47% in mice treated with NNK and 52% in urethane-treated mice. Markers of cell proliferation, apoptosis and angiogenesis were studied by immunohistochemical staining. Treatment with PFE caused significant reduction in Ki-67, proliferating cell nuclear antigen (PCNA), caspase-3, CD-31 and vascular endothelial growth factor (VEGF) in lungs of mice treated with NNK and urethane. Thus, our results show that PFE can act as a chemopreventive agent in smokers and ex-smokers with early lung lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 951.