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Morin augments anticarcinogenic and antiproliferative efficacy against 7,12-dimethylbenz(a)-anthracene induced experimental mammary carcinogenesis

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Abstract

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.

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Abbreviations

DMBA:

7,12-Dimethylbenz(a)-anthracene

TEBs:

Terminal end buds

AFP:

Alpha-feto protein

CEA:

Carcinoembryonic antigen

CA 15-3:

Cancer antigen 15-3

AgNOR:

Argyrophilic nucleolar proteins

PCNA:

Proliferating cell nuclear antigen

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Acknowledgments

The author, Ramadass Nandhakumar, is thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi, Government of India for providing grants in the form of Senior Research Fellowship (SRF) and the author, Salini Kombiyil, is thankful to Department of Biotechnology (DBT), New Delhi, and Government of India for supporting the grants in the form of Senior Research Fellowship (SRF).

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  1. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India

    Ramadass Nandhakumar, Kombiyil Salini & Sivasithambaram Niranjali Devaraj

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  1. Ramadass Nandhakumar
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Correspondence to Sivasithambaram Niranjali Devaraj.

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Nandhakumar, R., Salini, K. & Niranjali Devaraj, S. Morin augments anticarcinogenic and antiproliferative efficacy against 7,12-dimethylbenz(a)-anthracene induced experimental mammary carcinogenesis. Mol Cell Biochem 364, 79–92 (2012). https://doi.org/10.1007/s11010-011-1207-5

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