title: 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.
authors.affiliation: Centre of Advance Study in Zoology, Faculty of Science, Banaras Hindu University , Varanasi , India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.forename: Munendra Singh
authors.initials: MS
authors.lastname: Tomar
authors.forename: Arbind
authors.initials: A
authors.lastname: Acharya
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053119:Benzophenanthridines / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; C016299:chelerythrine; D053148:Caspase 3; D053453:Caspase 9; D019311:Staurosporine
keywords: Chelerythrine; Dalton lymphoma; apoptosis; p53-dependent/-independent