In general, oxidative stress resulting from an imbalance between prooxidant and antioxidant systems plays an important role in the pathogenesis of cancer. Morin (3,5,7,2',4'-pentahydroxyflavone), a member of the flavanol group, has been shown to possess chemopreventive potential against hepatocellular and colon cancer in experimental animals. Given the demonstrated importance of morin, aim of the present study was to evaluate the effect of morin on antiproliferative and anticarcinogenic effect against DMBA-induced experimental mammary carcinogenesis. Oral administration of 7,12-dimethylbenz(a)-anthracene (25 mg/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and nonenzymic antioxidants (reduced glutathione, vitamin C, and vitamin E). The levels of lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) and tumor markers such as CA 15-3, AFP and CEA in serum were increased significantly in cancer-induced animals as compared to control rats. Oral supplementation of morin at a dose of 50 mg/kg body weight significantly improved the body weight, enzymic, and nonenzymic antioxidants and considerably decreased the lipid peroxidation marker and tumor markers levels. Histological observations also correlated with the biochemical parameters. Tumor bearing animals showed marked increase in proliferating cell nuclear antigen-positive cells and also the number of AgNOR/nuclei compared with control rats while this expression levels were significantly reduced upon morin treatment. Thus, this study reveals the possible beneficial effect of morin as chemopreventive agent against the oxidative stress induced during mammary carcinogenesis.
Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of Hawthorn ( Crataegus oxyacantha ) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 mg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signalling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency and cancer growth inhibition at stem cell level can be expected.
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