title: Anti-tumor effect investigation of obtustatin and crude Macrovipera lebetina obtusa venom in S-180 sarcoma bearing mice.
abstract: Over the last few decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Isolated from the venom of Macrovipera lebetina obutusa (MLO), obtustatin represents the shortest known snake venom monomeric disintegrin specific inhibitor of α1β1 integrin. This low molecular weight peptide revealed a potent therapeutic effect on melanoma progression. Its oncostatic effect was related to the inhibition of angiogenesis. The aim of the proposed investigation was to study the influence of obtustatin and crude MLO venom on the S-180 sarcoma growth in vitro and in vivo. A S-180 sarcoma bearing mouse model, histological examination, DNA retardation assay were utilized to investigate the anti-tumor effects of MLO and obtustatin. In addition, some biochemical tests (chemiluminescence-ChL, TBA-test) were applied to elucidate the influence of obtustatin and crude MLO venom on the S-180 sarcoma. The size of tumor was significantly inhibited by MLO venom and obtustatin with the inhibitory rate of 50% and 33% at the doses of 10 µg/mouse and 1mg/kg/day respectively. Both ChL and MDA decrease in the two treated groups. Both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma. All our results have shown that both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma.
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia. Electronic address: naringhazaryan@gmail.com.
authors.forename: Narine A
authors.initials: NA
authors.lastname: Ghazaryan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Lusine A
authors.initials: LA
authors.lastname: Ghulikyan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Arsen V
authors.initials: AV
authors.lastname: Kishmiryan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Gayane R
authors.initials: GR
authors.lastname: Kirakosyan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Ofik H
authors.initials: OH
authors.lastname: Nazaryan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Tigran H
authors.initials: TH
authors.lastname: Ghevondyan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Naira A
authors.initials: NA
authors.lastname: Zakaryan
authors.affiliation: L.A. Orbeli Institute of Physiology NAS RA, Laboratory of Toxinology and Molecular Systematics, Orbeli Street 22, 0028 Yerevan, Armenia.
authors.forename: Naira M
authors.initials: NM
authors.lastname: Ayvazyan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D014757:Viper Venoms / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D014757:Viper Venoms; C474313:obtustatin, Vipera lebetina obtusa; D008315:Malondialdehyde; D004247:DNA
keywords: DNA; MLO venom; Obtustatin; S-180 sarcoma