Morin accelerates proliferative inhibition via NF-κB mediated transcriptional regulation of apoptotic events during chemical carcinogen induced mammary cancer in rats

Chemoprevention plays pivotal role in the prevention of human cancers. Morin, a bioflavonoid, has been known for its chemopreventive activities against various cancers and also in recent years, numerous investigations have shown that flavonol containing compounds induce apoptosis in various types of cancers in experimentally induced animal models. Thus the present study was aimed to understand the molecular pathway of inflammation mediated apoptosis regulation is of crucial importance for developing therapeutic agents for the intervention of mammary cancer. In this study, we investigated the protective effects of morin on DMBA-induced mammary carcinoma in Sprague-Dawley rats. Results showed that morin significantly attenuated DMBA-induced inflammation mediated apoptotic cell death. Morin effectively suppressed the down-regulation of bax and up-regulation of bcl-2. Furthermore, morin down-regulated the pro-inflammatory markers such as COX-2, NFkB, TNF-α, IL-2, and IL-1β. We also demonstrated that intrinsic mitochondrial mediated apoptotic events by morin was associated with the release of cytochrome C and apoptotic signaling pathway. Therefore, these results suggest that morin can prevent mammary carcinoma under DMBA-induced conditions by inducing cancer cell death through apoptotic events and thus suggest that it may be clinically evaluated for the chemoprevention of mammary carcinoma.