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, Prabhu and Vijay Avin, B. R. and Vigneshwaran, V. and Prashanth Kumar, M. V. and Abhishek, T. S. and Lakshmi , R. V. and Khanum, Shaukath Ara 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 & Pharmacotherapy, 68 (6). pp. 791-797. ISSN 0753-3322

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Official URL: http://dx.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
Additional Information: Unmapped bibliographic data: PY - 2014/7// [EPrints field already has value set] JO - Biomedicine & Pharmacotherapy [Field not mapped to EPrints]
Uncontrolled Keywords: DAO-9, Murine carcinoma, Caspase-3, p53, Bax
Subjects: Physical Sciences > Chemistry
Divisions: Constituent Colleges > Yuvaraja's College Mysore > Chemistry
Depositing User: Ms. Manjula p
Date Deposited: 05 Nov 2014 11:00
Last Modified: 15 Jul 2016 10:37
URI: http://eprints.uni-mysore.ac.in/id/eprint/17201

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