title: DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma.
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.
authors.affiliation: Department of Chemistry, Yuvaraja's College (Autonomous), University of Mysore, Mysore 570 006, Karnataka, India.
authors.forename: H D
authors.initials: HD
authors.lastname: Gurupadaswamy
authors.affiliation: Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577 203, Karnataka, India.
authors.forename: P
authors.initials: P
authors.lastname: Thirusangu
authors.affiliation: Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577 203, Karnataka, India.
authors.forename: B R
authors.initials: BR
authors.lastname: Vijay Avin
authors.affiliation: Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577 203, Karnataka, India.
authors.forename: V
authors.initials: V
authors.lastname: Vigneshwaran
authors.affiliation: Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577 203, Karnataka, India.
authors.forename: M V
authors.initials: MV
authors.lastname: Prashanth Kumar
authors.affiliation: Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577 203, Karnataka, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Abhishek
authors.affiliation: Department of Chemistry, Yuvaraja's College (Autonomous), University of Mysore, Mysore 570 006, Karnataka, India.
authors.forename: V
authors.initials: V
authors.lastname: Lakshmi Ranganatha
authors.affiliation: Department of Chemistry, Yuvaraja's College (Autonomous), University of Mysore, Mysore 570 006, Karnataka, India.
authors.forename: S A
authors.initials: SA
authors.lastname: Khanum
authors.affiliation: Molecular Biomedicine Laboratory, Post Graduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577 203, Karnataka, India. Electronic address: pbtssc@gmail.com.
authors.forename: B T
authors.initials: BT
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D051379:Mice; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D010069:Oxadiazoles; D016159:Tumor Suppressor Protein p53; D004720:Endonucleases; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Bax; Caspase-3; DAO-9; Murine carcinoma; p53