Abstract
abstractBreast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2–5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.
Highlights
Breast cancer is the most frequently diagnosed cancer and the primary cause of cancer-related death in women worldwide [1]
While there were no visible tumors in the mammary glands of normal (Group A) as well as pomegranate emulsion (PE) (5.0 g/kg) control (Group F) rats, macroscopic mammary tumors of various sizes and shapes were detected in the mammary glands of all DMBA-exposed groups
PE at a dose of 0.2 g/kg (Group C) or 1.0 g/kg (Group D) exhibited 20% reduction in tumor incidence compared to the DMBA control, but the results did not reach the level of statistical significance
Summary
Breast cancer is the most frequently diagnosed cancer and the primary cause of cancer-related death in women worldwide [1]. In the United States, an average woman has a 1 in 8 lifetime risk of breast cancer [2]. About 233,000 new cases of breast cancer and 40,000 deaths due to this disease have been estimated to occur in women in the United States in 2014 [3]. The estimated cost of breast cancer management in the United States is about 16.5 billion dollars per year and this cost is more than any other cancer [4]. Risk factors of breast cancer include age, family history, and genetic abnormalities, such as mutations in tumor suppressor genes BRCA1 and BRCA2 [5]. Various life style-related factors, such as alcohol consumption and obesity, and disease conditions (e.g., diabetes), contribute to the occurrence of breast cancer [7,8,9,10]
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