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Isolation, Characterization and Mechanism of Action of Anticancer Compounds from Selected Plant Sources.

Smitha, J. (2012) Isolation, Characterization and Mechanism of Action of Anticancer Compounds from Selected Plant Sources. PhD thesis, University of Mysore.

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Abstract

Cancer is a deadly disease and results from several interconnected processes such as including cell proliferation, angiogenesis, cell adhesion, migration, and invasion into the surrounding tissue etc. The appearance of metastases in organs/distant from the primary tumor is the most destructive feature of cancer. Thus metastasis remains as the principal cause of the death of cancer patients despite decades of research that are aimed at restricting the tumor growth. Therefore, current thesis entitled “Isolation, characterization and mechanism of action of anticancer compounds from selected plant sources” explores the possibility of dietary antioxidants and antimetastatic polysaccharides that can effectively bring down oxidative stress and galectin-3, a key molecule in metastasis, which causes severity of cancer pathogenicity and death as revealed in scheme – 1. During the study, series of commonly used plant/dietary sources were screened for inhibition of H+, K-ATPase, antioxidant and antimetastatic cyto/DNA protective activity. A. serpyllifolia and Zea mays were selected as a potent source of antioxidantants and antimetastatic pectic polysaccharides respectively from Corn – Zea mays were characterized and determined their efficacy in vitro and in vivo. Separation of free (ASFP) and bound phenolic (ASBP) fractions from A.serpyllifolia followed by demonstration of differential antioxidant activity of phenolic acid composition in them enabled us to correlate the key role and involvement of phenolic acids against various steps of reactive oxygen species mediated cancer pathogenecity. The content and nature of phenolic acids in the phenolic fractions therefore may explain their antioxidant and antiproliferative abilities to be responsible for anticancer property. A.serpyllifolia also found to contain andrographolide (AG) contributing to the activity. Results of the study clearly indicated the inhibition of metastatic cell growth; inhibition of cell adhesion/invasion, inhibition of tumor colony formation etc by corn pectic polysaccharide (COPP). Evaluation of molecules involved in cancer metastasis such as upregulated galectin-3, matrix metalloproteinases, phosphoglucoisomerase (PGI) and NFkB were modulated by selected dietary galectin-inhibitors. Studies are thus evidenced the potential inhibition of cascades of metastatic events induced by galectin-3. Structure – function analysis revealed the presence of higher levels of galactose and arabinose and their probable contribution to antimetastatic potency. Antioxidants of A.serpyllifolia and antimetastatic COPP was effective in inhibiting Reactive oxygen species - mediated stomach cancer by N- methyl N- nitrosourea and B16F10 melanoma cells induced lung metastasis in vivo, suggesting their in vivo efficacy against cancer. Overall data thus suggest that selected sources A. serpyllifolia and Zea mays having both antioxidants and antimetastatic components can effectively inhibit cancer spread/metastasis at multistep (Scheme-1). Thus the study highlights the need for multi-targetting components for successful inhibition or arrest of cancer/cancer metastasis.

Item Type: Thesis (PhD)
Uncontrolled Keywords: anticancer compounds, selected plant sources, A. serpyllifolia, Zea mays
Subjects: 500 Natural Sciences and Mathematics > 10 Plants
600 Technology > 01 Medical sciences
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 04 Mar 2014 05:24
Last Modified: 04 Mar 2014 05:24
URI: http://ir.cftri.com/id/eprint/11361

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