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A Heat Stable Protein Toxin (drCT-I) from the Indian Viper (Daboia russelli russelli) Venom having Antiproliferative, Cytotoxic and Apoptotic Activities

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Title A Heat Stable Protein Toxin (drCT-I) from the Indian Viper
(Daboia russelli russelli) Venom having Antiproliferative,
Cytotoxic and Apoptotic Activities
 
Creator Gomes, Antony
Roy Choudhury, Subhasree
Saha, Archita
Mishra, R
Giri, Biplab
Biswas, A K
Debnath, Anindita
Gomes, Aparna
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description A heat stable 7.2 kDa protein toxin (drCT-I) has been purified and crystallized from Indian Daboia russelli russelli
venom (Roy Choudhury et al., 2006. Acta Cryst. F Struct Biol Cryst Commun, 62(Pt. 3), 292). The N-terminal (first 20)
amino acid sequence of drCT-I was LKCNKLVPLFYKTCPAGKNL, which showed sequence homology to cytotoxins
isolated from Naja venom. drCT-I has been evaluated for anticancer activity against EAC cells in vivo and human
leukemic cells (U937, K562) in vitro. drCT-I (125 mg/kg, i.p/day for 10 days) significantly decreased EAC cell count, cell
viability (po0:001) and significantly increased the survival time of tumour bearing mice (T/C% 178.64, po0:01) in
comparison to untreated tumour bearing control. drCT-I, produced dose and time-dependent inhibition of U937 and K562
cell growth and had an IC50 of 8.9 and 6.7 mg/ml respectively after 24 h treatment. The reduced MTT values after drCT-I
treatment indicated its cytotoxic nature, which supported its antiproliferative action. Scanning electron microscopy and
confocal microscopy in U937 and K562 cells after drCT-I treatment indicated certain features of apoptosis such as
membrane blebbing, perforations, nuclear fragmentation. The induction of apoptosis was further confirmed by
phosphatidylserine externalization observed using annexinV-FITC/PI staining and flow cytometric analysis. drCT-I
brought about apoptosis by G1 phase arrest of the cell cycle. The effect of drCT-I on normal human peripheral blood
mononuclear cell (PBMNC) viability and cytotoxicity was studied in culture and was found to be lower than that on U937
and K562 cells. Thus both in vivo and in vitro experimental results suggested that drCT-I possessed anticancer potential.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1157/1/TOXICON_49_(1)46%2D56;2007[127].pdf
Gomes, Antony and Roy Choudhury, Subhasree and Saha, Archita and Mishra, R and Giri, Biplab and Biswas, A K and Debnath, Anindita and Gomes, Aparna (2007) A Heat Stable Protein Toxin (drCT-I) from the Indian Viper (Daboia russelli russelli) Venom having Antiproliferative, Cytotoxic and Apoptotic Activities. Toxicon, 49 (1). pp. 46-56.
 
Relation http://dx.doi.org/10.1016/j.toxicon.2006.09.009
http://www.eprints.iicb.res.in/1157/