Pro-apoptotic activity of imidazole derivatives mediated by up-regulation of Bax and activation of CAD in Ehrlich Ascites Tumor cells.
In this study we report that, imidazole derivatives can induce apoptosis in Ehrlich ascites tumor (EAT) cells, which is clearly evident from annexin-V staining, flow cytometric analysis of cell cycle phase distribution and DNA fragmentation. Delineating further into molecular mechanisms leading to apoptosis of EAT cells, we observed that imidazole derivatives induce tumor cell death by the up-regulation of proto-oncoprotein Bax, release of cytochrome c from the mitochondria which activates caspase-3 and activated caspase-3 activates CAD (Caspase Activated DNase) causes DNA fragmentation. The status of Bcl-2 remains unaltered in EAT cells, and the under expression of Bcl-2 and up-regulation of Bax resulted in the increase of Bax: Bcl-2 ratio suggesting that Bcl-2 family involved in the control of apoptosis. These results suggest a further possible clinical application of imidazole derivatives as pro-apoptotic agent in association with conventional chemotherapeutic agents.
Kumar
C Anil
CA
Department of Studies in Applied Botany and Biotechnology, University of Mysore, 570006 Manasagangotri, Mysore, India.
Jayarama
Shankar
S
Basappa
Salimath
Bharathi P
BP
Rangappa
Kanchugarakoppal S
KS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002286:Carcinoma, Ehrlich Tumor; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D021381:Protein Transport; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D007093:Imidazoles; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; D053148:Caspase 3