Potential Anticancer Activity of Caspian Cobra Venom Through Induction of Oxidative Stress in Glioblastoma Cell Line
- 48 Downloads
Despite advances in therapeutic strategies in the management of cancer, malignant glioma remains difficult to treat due to progressive resistance to conventional drugs. New studies made efforts to develop new anticancer agents from the screening of natural compounds. The biodiversity of venoms and their bioactive toxins makes them a special source for the development of novel therapeutic agents. The aim of the present study was to investigate the effect of Naja naja oxiana (NNO) crude venom on U87MG glioma cell line. Cellular viability and the generated amount of reactive oxygen species were determined by MTT and redox-sensitive dye DCFH-DA, respectively. A dose-dependent decline in viability of cells along with increase in generation of reactive oxygen species (ROS) occurred after the 24-h exposure to NNO venom. Incubation of RBC with NNO venom for 24 h indicated that hemolysis was not more than 6%. The results showed that NNO venom might act through the production of excess ROS, further disruption of mitochondrial function, and decrease in viability of U87MG without changes in the integrity of RBC membrane. However, more investigations are needed to find out detailed mechanisms by which NNO venom inhibits the viability of U87MG.
KeywordsCaspian cobra venom Naja naja oxiana U87MG glioma cell line Cytotoxicity Reactive oxygen species
The authors gratefully acknowledge the financial support (Project No.: 96000311) of the Kerman University of Medical Sciences.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro-oncology 15(Suppl 2):ii1–ii56. https://doi.org/10.1093/neuonc/not151 CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, Wrensch MR, Barnholtz-Sloan JS (2014) The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncology 16(7):896–913. https://doi.org/10.1093/neuonc/nou087 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Song JK, Jo MR, Park MH, Song HS, An BJ, Song MJ, Han SB, Hong JT (2012) Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor kappaB and signal transducer and activator of transcription 3. Arch Pharmacal Res 35(5):867–876. https://doi.org/10.1007/s12272-012-0512-1 CrossRefGoogle Scholar
- 10.Fakhri A, Omranipour R, Fakhri S, Mirshamsi M, Zangeneh F, Vatanpour H, Pourahmad J (2017) Naja naja oxiana venom fraction selectively induces ROS-mediated apoptosis in human colorectal tumor cells by directly targeting mitochondria. Asian Pac J Cancer Prev APJCP 18(8):2201–2208. https://doi.org/10.22034/APJCP.2017.18.8.2201 CrossRefPubMedGoogle Scholar
- 11.Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48(6):749–762. https://doi.org/10.1016/j.freeradbiomed.2009.12.022 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Rucavado A, Escalante T, Gutierrez JM (2004) Effect of the metalloproteinase inhibitor batimastat in the systemic toxicity induced by Bothrops asper snake venom: understanding the role of metalloproteinases in envenomation. Toxicon 43(4):417–424. https://doi.org/10.1016/j.toxicon.2004.01.016 CrossRefPubMedGoogle Scholar
- 16.Gasanov SE, Shrivastava IH, Israilov FS, Kim AA, Rylova KA, Zhang B, Dagda RK (2015) Naja naja oxiana cobra venom cytotoxins CTI and CTII disrupt mitochondrial membrane integrity: implications for basic three-fingered cytotoxins. PLoS One 10(6):e0129248. https://doi.org/10.1371/journal.pone.0129248 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Machado ART, Aissa AF, Ribeiro DL, Hernandes LC, Machado CS, Bianchi MLP, Sampaio SV, Antunes LMG (2017) The toxin BjussuLAAO-II induces oxidative stress and DNA damage, upregulates the inflammatory cytokine genes TNF and IL6, and downregulates the apoptotic-related genes BAX, BCL2 and RELA in human Caco-2 cells. Int J Biol Macromol 109:212–219. https://doi.org/10.1016/j.ijbiomac.2017.12.015 CrossRefPubMedGoogle Scholar
- 23.Pawelek PD, Cheah J, Coulombe R, Macheroux P, Ghisla S, Vrielink A (2000) The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site. EMBO J 19(16):4204–4215. https://doi.org/10.1093/emboj/19.16.4204 CrossRefPubMedPubMedCentralGoogle Scholar