title: Cytotoxic and antioxidant property of a purified fraction (NN-32) of Indian Naja naja venom on Ehrlich ascites carcinoma in BALB/c mice.
abstract: A cytotoxic and antioxidant protein (NN-32) from the Indian spectacled cobra Naja naja venom was identified and its probable mode of action on murine Ehrlich ascites carcinoma (EAC) was established. The venom purified through ion exchange chromatography produced several peaks, among which fraction 32 produced cytotoxic-cardiotoxic properties. This fraction (NN-32) showed a single peak (retention time 38.3 min) by HPLC using C4 column. The molecular mass determined by MALDI-MS, found to be 6.7 kDa and the first ten N-terminal sequence was determined (LKCNKLVPLF) by Edmann degradation method using applied Biosystem procise sequencer. It was observed that the sequence shared 100% homology with other cytotoxin cardiotoxin identified from the venom of Naja species. NN-32 showed cytotoxicity on EAC cells, increased survival time of inoculated EAC mice, reduced solid tumor volume and weight. NN-32 increased proapoptotic protein caspase 3 and 9 activity and Bax-Bcl2 ratio. It also increased the antioxidant markers glutathione, glutathione peroxidase, glutathione transferase, superoxide dismutase and catalase activity. NN-32 increased serum IL-10 level and decreased murine keratinocyte-derived chemokine level. The cardiotoxicity of NN-32 was established on isolated guinea pig auricle, where 100% irreversible blockade of auricular contraction was observed. Thus, it may be concluded that, NN-32 induced anticancer activity in EAC mice was partly mediated through its apoptogenic - antioxidant property.
authors.affiliation: Drug Development/Diagnostics & Biotechnology Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, West Bengal, India.
authors.forename: Tanaya
authors.initials: T
authors.lastname: Das
authors.forename: Shamik
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Babli
authors.initials: B
authors.lastname: Halder
authors.forename: Archita
authors.initials: A
authors.lastname: Biswas
authors.forename: Shubho
authors.initials: S
authors.lastname: Das Gupta
authors.forename: Antony
authors.initials: A
authors.lastname: Gomes
authors.forename: Aparna
authors.initials: A
authors.lastname: Gomes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004546:Elapid Venoms / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D003603:Cytotoxins; D004546:Elapid Venoms