Articulatin-D induces apoptosis via activation of caspase-8 in acute T-cell leukemia cell line
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Leukemia is among the most aggressive and prevalent human malignant carcinoma. Chemotherapy is the preferred therapeutic strategy; however, recurrence of cancer and non-selective cytotoxicity are the major concerns. Unlike synthetic chemotherapeutic agents, mistletoe ribosome-inactivating protein (RIP) displays anti-tumor function in various types of cancers. However, its effect on leukemia cells is little explored. In this study, we assessed the impact of Viscum articulatum RIP (Articulatin-D) on the survival of acute T-cell leukemia cells and the involved molecular and cellular mechanisms. Cell proliferation assay showed that Articulatin-D suppressed the viability of leukemia cells selectively. We further confirmed that the elevation of mitochondrial membrane potential and exposure of phosphatidylserine are the early events of apoptosis induction in Articulatin-D-treated Jurkat cells. Subsequently, we found that Articulatin-D treatment induces apoptosis in Jurkat cells in a time- and concentration-dependent manner. In conclusion, we provided evidence that Articulatin-D efficiently activates caspase-8 involved in extrinsic pathway of apoptosis induction, which ultimately results in caspase-3-dependent DNA fragmentation of Jurkat cells. Further evaluation of Articulatin-D in cell culture and animal models may provide novel information on selective cytotoxicity to acute T-cell leukemia and its involvement in targeting tumor cell survival pathways.
KeywordsViscum articulatum (mistletoe) Anticancer Ribosome-inactivating protein Apoptosis mechanism Leukemia cell line Articulatin-D
Authors thank the University of Delhi for Faculty research grant to VM, Miranda House for Flow Cytometer facility of the DS Kothari Centre for Research and Innovation in Science Education. RM thanks the University Grant Commission for JRF for Ph.D. and SS thanks the UGC for Non-NET Research Fellowship. Authors thank Professor Millind Sardesai for all support throughout the study.
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