Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice Academic Article uri icon

abstract

  • This study investigated the potential role of the p70S6K1/HIF1 axis in the anti-inflammatory activities of pomegranate (Punica granatum L.) polyphenolics in dextran sodium sulfate (DSS)-induced colitis in Sprague-Dawley rats and in lipopolysaccharide (LPS)-treated CCD-18Co colon-myofibroblastic cells. Rats were administered either control (CT) or pomegranate beverage (PG), containing ellagic acid and ellagitannins, then exposed to three cycles of 3% DSS followed by a 2-week recovery period. PG protected against DSS-induced colon inflammation and ulceration (50% and 66.7%, P=.05 and .045, respectively), and decreased the Ki-67 proliferative index in the central and basal regions compared to the control. PG also significantly reduced the expression of proinflammatory cytokines (TNF- and IL-1), COX-2, and iNOS at mRNA and protein levels. In addition, the expression of p70S6K1 and HIF1 was reduced, while the tumor suppressor miR-145 was induced by PG. The intestinal microbiota of rats treated with PG showed a significant increase in Ruminococcaceae that include several butyrate producing bacteria (P=.03). In vitro, PG reduced the expression of p70S6K1 and HIF1 and induced miR-145 in a dose-dependent manner. The involvement of miR-145/p70S6K1 was confirmed by treating LPS-treated CCD-18Co cells with miR-145 antagomiR, where the pomegranate polyphenolics reversed the effects of the antagomiR for p70S6K1 mRNA and protein levels. These results suggest that pomegranate polyphenols attenuated DSS-induced colitis by modulating the miR-145/p70S6K/HIF1 axis, indicating potential use in therapeutic treatment of ulcerative colitis.

published proceedings

  • J Nutr Biochem

altmetric score

  • 9.25

author list (cited authors)

  • Kim, H., Banerjee, N., Sirven, M. A., Minamoto, Y., Markel, M. E., Suchodolski, J. S., Talcott, S. T., & Mertens-Talcott, S. U.

citation count

  • 44

complete list of authors

  • Kim, Hyemee||Banerjee, Nivedita||Sirven, Maritza A||Minamoto, Yasushi||Markel, Melissa E||Suchodolski, Jan S||Talcott, Stephen T||Mertens-Talcott, Susanne U

publication date

  • January 2017