Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8545663 | Chemico-Biological Interactions | 2016 | 25 Pages |
Abstract
Ruviprase, a 4.4 kDa peptide isolated from Daboia russelii russelii venom demonstrated antiproliferative activity against EMT6/AR1, U-87MG, HeLa and MCF-7 cancer cells with an IC50 value of 23.0, 8.8, 5.8 and 4.0 μg mlâ1, respectively. However, it was nontoxic to non-cancerous human embryonic kidney cell and human peripheral blood lymphocytes. Flow-cytometric analysis confirmed the apoptosis induction in MCF-7 cells by Ruviprase where it induced DNA condensation but did not cause mitotic blockage or chromosomal aberration in treated-cells. Immunofluorescence microscopic analysis indicated Ruviprase induced apoptosis in MCF-7 cells through p53 and p21-mediated pathways. Ruviprase generated reactive oxygen species (ROS), altered the mitochondrial transmembrane potential, and significantly decreased the cellular glutathione (GSH) content of MCF-7 cells. Immunoblotting and quantitative real-time PCR (qRT-PCR) analyses suggested that Ruviprase down-regulated the expression of anti-apoptotic protein Bcl-2, increased cleavage of poly (ADP-ribose) polymerase (PARP) protein, and up-regulated the expression of pro-apoptotic protein Bax, as well as executer protein caspase-7 to induced apoptosis in MCF-7 cells via intrinsic pathway. This is the first report on the characterization of the anticancer potential of a small, non-toxic and anticoagulant peptide purified from Russell's viper venom.
Keywords
EMEMPBSRVVp53DICPARPGSHHPBLqRT-PCRBSAROSbovine serum albuminRussell's viper venomEagle's minimal essential mediumApoptosisPhosphate buffered salineHuman peripheral blood lymphocytesMitochondrial pathwayquantitative real-time PCRPropidium iodidepoly (ADP-ribose) polymeraseAnticancer peptideCaspase-7differential interference contrastReactive oxygen species
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Authors
Rupamoni Thakur, Sudarshan Kini, Sillarine Kurkalang, Atanu Banerjee, Purba Chatterjee, Abhishek Chanda, Anupam Chatterjee, Dulal Panda, Ashis K. Mukherjee,