DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma

Gurupadaswamy, H. D. and Thirusangu, P. and Vijay Avin, B. R. and Vigneshwaran, V. and Prashanth Kumar, M. V. and Abhishek, T. S. and Lakshmi Ranganatha, V. and Khanum, S. A. and Prabhakar, B. T. (2014) DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma. Biomedicine and Pharmacotherapy, 68 (6). pp. 791-797. ISSN 0753-3322

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Official URL: https://doi.org/10.1016/j.biopha.2014.07.004

Abstract

One of the main strategies to inhibit the tumor growth is to promote the biochemical events leading to DNA degradation, which would eventually culminate in apoptosis. We have earlier reported that the 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole(DAO-9) possessed anti-cancer activity. To address the exact molecular mechanism underlying anti-cancer property, present study focused on evaluating the anti-tumor effect of the DAO-9 on murine ascites carcinoma cells using various in vivo and in vitro assays. The in vivo assays implicated a strong regression in tumor growth of ascites carcinoma after treatment which is due to apoptogenic efficacy as assessed through structural morphology of EAC cells by Giemsa, Acridine orange, Annexin V staining and FACS analysis. Nucleosomal DNA fragmentation induced by DAO-9 is due to activation of caspase-3 mediated DNAse as verified by endonuclease assays and immunoblot analysis. The caspase-3 activation mechanism is by induction of intrinsic cascade signaling molecules, such as p53, Bax, Bad and cytochrome c (cyt c) expression as verified by western blot. The results concluded that the tumor inhibiting activity of DAO-9 is due to activation of the apoptotic signaling cascade, which could be translated into targeted anti-cancer drug in the near future.

Item Type: Article
Uncontrolled Keywords: 3, animal experiment, animal model, antineoplastic activity, antineoplastic agent, apoptosis, Article, controlled study, in vitro study, in vivo study, mouse, nonhuman, unclassified drug, animal, Animals, chemistry, biosynthesis, cancer inhibition, female, Female, metabolism, pathology, protein expression, tumor growth, enzyme activity, physiology, enzymology, Western blotting, cell proliferation, Apoptosis, caspase 3, protein BAD, acridine orange, signal transduction, oxadiazole derivative, Oxadiazoles, protein Bax, immunoblotting, Mice, Carcinoma, drug effects, endonuclease, cell structure, enzyme activation, Enzyme Activation, DNA fragmentation, protein p53, Ehrlich Tumor, ascites tumor, Caspase 3, cytochrome c, Tumor Suppressor Protein p53, 2, 4 oxadiazole, 5 di(4 aryloylaryloxymethyl) 1, ascites tumor cell, cancer regression, Casp3 protein, deoxyribonuclease, Endonucleases, fluorescence activated cell sorting, lipocortin 5
Subjects: C Chemical Science > Chemistry
Divisions: Yuvaraj college > Chemistry
Depositing User: Arshiya Kousar
Date Deposited: 20 Jun 2019 09:57
Last Modified: 20 Jun 2019 09:57
URI: http://eprints.uni-mysore.ac.in/id/eprint/3509

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