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Pro-apoptotic activity of imidazole derivatives mediated by up-regulation of Bax and activation of CAD in Ehrlich Ascites Tumor cells

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Summary

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.

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Acknowledgements

The authors acknowledge the financial support from Department of Biotechnology, New Delhi, India and CSIR, Government of India for financial support under the project vide no 01(1904)/03/EMR-I.

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Authors and Affiliations

  1. Department of Studies in Applied Botany and Biotechnology, University of Mysore, 570006, Manasagangotri, Mysore, India

    C. Anil Kumar, Shankar Jayarama & Bharathi P. Salimath

  2. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570006, India

    Basappa & Kanchugarakoppal S. Rangappa

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  1. C. Anil Kumar
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  2. Shankar Jayarama
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Correspondence to Kanchugarakoppal S. Rangappa.

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Anil Kumar, C., Jayarama, S., Basappa et al. Pro-apoptotic activity of imidazole derivatives mediated by up-regulation of Bax and activation of CAD in Ehrlich Ascites Tumor cells. Invest New Drugs 25, 343–350 (2007). https://doi.org/10.1007/s10637-006-9033-4

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