title: Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.
abstract: Breast 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.
authors.affiliation: a Department of Pharmaceutical Sciences , College of Pharmacy, Larkin Health Sciences Institute , Miami , Florida , USA.
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.affiliation: b Department of Pharmaceutical Sciences , College of Pharmacy, Northeast Ohio Medical University , Rootstown , Ohio , USA.
authors.forename: Animesh
authors.initials: A
authors.lastname: Mandal
authors.affiliation: c School of Health Sciences, University of Turabo , Gurabo , Puerto Rico.
authors.forename: Piyali
authors.initials: P
authors.lastname: Bhattacharyya
authors.affiliation: d Department of Pharmacogenomics , Bernard J. Dunn School of Pharmacy, Shenandoah University , Ashburn , Virginia , USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatia
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D029561:Lythraceae / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016588:Anticarcinogenic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D015127:9,10-Dimethyl-1,2-benzanthracene