Activation of p53-dependent/-independent pathways of apoptotic cell death by chelerythrine in a murine T cell lymphoma

Abstract

The p53 tumor suppressor protein has been implicated as an activator of apoptosis. In order to investigate the effect of chelerythrine and staurosporine on the activation of p53-dependent/-independent pathways of Dalton lymphoma (DL) cell death, cells were treated with chelerythrine and staurosporine for 1 h, 3 h and 6 h, respectively. It was found that treatment with chelerythrine and staurosporine increased the expression of total-p53/phospho-53 (ser-15) significantly at protein and mRNA levels, which resulted in activation of the p53-dependent apoptotic pathway in DL cells. In addition, increased activities of cyt-c, caspase-9 and caspase-3 and degradation of DNA into fragments confirmed activation of the p53-independent apoptotic pathway in p53 knockdown RNAi-DL cells. In brief, the present study demonstrated activation of p53-dependent/-independent apoptotic pathways in DL cells. Therefore, targeting of p53-dependent/-independent apoptotic pathways may lead to the possibility of designing and developing better therapeutic regimens to treat DL and other human cancers.

Keywords::

• Chelerythrine
• Dalton lymphoma
• p53-dependent/-independent
• apoptosis

Acknowledgements

The authors are thankful to Professor and Coordinator S. M. Singh, Department of Biotechnology, and Dr. S. K. Chaube, Department of Zoology, Banaras Hindu University, Varanasi for providing fluorescence microscopy. Special thanks go to Mrs. Sabana, DRDO, Kolkata for her kind help in the caspase assay.

The project was supported by the University Grants Commission (UGC), New Delhi. Mr. Sanjay Kumar expresses his sincere thanks to the Indian Council of Medical Research (ICMR), New Delhi for student support.

Potential conflict of interest

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