title: Articulatin-D induces apoptosis via activation of caspase-8 in acute T-cell leukemia cell line.
abstract: 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.
authors.affiliation: Bioresources and Environmental Biotechnology Laboratory, Department of Environmental Studies, University of Delhi, Delhi, 110 007, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Bioresources and Environmental Biotechnology Laboratory, Department of Environmental Studies, University of Delhi, Delhi, 110 007, India.
authors.forename: Mrinal K
authors.initials: MK
authors.lastname: Das
authors.affiliation: Bioresources and Environmental Biotechnology Laboratory, Department of Environmental Studies, University of Delhi, Delhi, 110 007, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Bioresources and Environmental Biotechnology Laboratory, Department of Environmental Studies, University of Delhi, Delhi, 110 007, India.
authors.forename: Radhey Shyam
authors.initials: RS
authors.lastname: Sharma
authors.affiliation: Department of Zoology, Miranda House College, University of Delhi, Delhi, 110 007, India.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Bioresources and Environmental Biotechnology Laboratory, Department of Environmental Studies, University of Delhi, Delhi, 110 007, India. mistletoe_h@hotmail.com.
authors.forename: Vandana
authors.initials: V
authors.lastname: Mishra
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054790:Ribosome Inactivating Proteins, Type 2 / Q000737:chemistry / Q000494:pharmacology*; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology*; D028181:Viscum / Q000737:chemistry*
chemical_list: D028321:Plant Preparations; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: Anticancer; Apoptosis mechanism; Articulatin-D; Leukemia cell line; Ribosome-inactivating protein; Viscum articulatum (mistletoe)