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Chem Biol Interact. 2016 Oct 25;258:297-304. doi: 10.1016/j.cbi.2016.09.004. Epub 2016 Sep 6.

Mechanism of apoptosis induction in human breast cancer MCF-7 cell by Ruviprase, a small peptide from Daboia russelii russelii venom.

Author information

1
Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur 784028, Assam, India.
2
Department of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai 400076, Maharashtra, India.
3
Molecular Genetics Laboratory, Department of Biotechnology and Bioinformatics, North-Eastern Hill University, Shillong 793022, Meghalaya, India.
4
Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur 784028, Assam, India. Electronic address: akm@tezu.ernet.in.

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 ml(-1), 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:

Anticancer peptide; Apoptosis; Caspase-7; Mitochondrial pathway; Pro-apoptotic protein; p53

PMID:
27613483
DOI:
10.1016/j.cbi.2016.09.004
[Indexed for MEDLINE]

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