Abstract 5447: Breast cancer chemoprevention by ‘Jamun’, the Indian blackberry: Potential mechanisms

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.5447-5447
• Main Authors: Aqil, Farrukh, Jeyabalan, Jeyaprakash, Munagala, Radha, Ravoori, Srivani, Sharma, Ramjee, Sidana, Jasmeen, Singh, Inder P., Gupta, Ramesh C.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-5447

Dark-colored berries are gaining increasing attention lately for their chemopreventive and chemotherapeutic activities. Jamun (Syzygium cumini L.), the Indian blackberry is perhaps the only berry that has the diversity of anthocyanins of blueberry and abundance of ellagic acid present in black raspberry. We previously reported chemoprotective activities in jamun pulp extract and powder in vitro and short-term in vivo studies (Aqil et al. AACR 2010, Vol. 51, Abst. # 5688). Here we report anti-cancer potential of jamun pulp powder against estrogen mediated breast cancer and the role of miRNAs and other targets in the disease inhibition. Groups of female ACI rats were given AIN-93M diet or diet supplemented with jamun pulp powder (5%, w/w). Two weeks later, animals from each group were treated with subcutaneous silastic implants of 17β-estradiol (1.2 cm; 9 mg). Additional groups of animals received control or experimental diet in the absence of estrogen. Diet and water were provided ad libitum. Twelve weeks later animals were palpated weekly for the mammary tumors, and all groups were euthanized when tumors incidence reached over 90% in control group. Compared to control, jamun-supplemented diet delayed the first tumor appearance by 21 days, and significantly reduced the tumor incidence (65% vs 96%), tumor burden (313±95 vs 661±123 mm3) and tumor multiplicity (1.8±0.3 vs 4.2±0.4 tumors/rat). The experimental diet also significantly reduced the estrogen-associated growth of pituitary prolactinomas, circulating prolactin and estradiol levels and the mammary cell proliferation (PCNA) markers. Mechanistically, the jamun diet significantly offset estrogen-associated increases in mammary cell proliferation, ER-α and cyclin D1 as determined by western blot analysis. We have recently identified ‘miRNA signature’ associated with estrogen treatment (Munagala et al. AACR 2011, Vol. 52, Abst. # 155). All miRNAs that were either significantly overexpressed (miR-182 and miR-375) or underexpressed (miR-127 and miR-206) as a result of estrogen treatment were significantly protected by intervention with the jamun diet. Targets for these miRNAs remain to be identified. Together, our data show that jamun significantly offset estrogen-mediated alterations in i) mammary cell proliferation; ii) ER-α; iii) cyclin D1, and iv) candidate miRNAs, and that the modulation of these biomarkers correlated with the reduction in mammary carcinogenicity. (Supported by CA-125152, CA-118114 and