25 March, 2011

Odontobuthus doriae venom as cancer medicine

Scorpions have been used in traditional medicine since ancient times, and in the last decade there have been a lot of research into scorpion venom to find potential agents to be used in medicine and treatment of serious diseases like cancer. Chlorotoxin from the venom of Leiurus quinquestriatus is one example of a very promising agent in the fight against serious brain cancer.

Jamil Zargan and co-workers have now showed that the venom of Odontobuthus doriae (Thorell, 1876) (Buthidae) induced apoptosis (programmed cell death) and inhibits DNA synthesis (inhibit cell growth and cell proliferation) in human neuroblastoma cells (Wikipedia on neuroblastoma). More investigations of the venom of this species are of course necessary, but the properties shown by the venom in this study will make it a valuable therapeutic agent in cancer research.

Scorpion and its organs have been used to cure epilepsy, rheumatism, and male impotency since medieval times. Scorpion venom which contains different compounds like enzyme and non-enzyme proteins, ions, free amino acids, and other organic inorganic substances have been reported to posses antiproliferative, cytotoxic, apoptogenic, and immunosuppressive properties. We for the first time report the apoptotic and antiproliferative effects of scorpion venom (Odontobuthus doriae) in human neuroblastoma cells. After exposure of cells to medium containing varying concentrations of venom (10, 25, 50, 100, and 200 lg/ml), cell viability decreased to 90.75, 75.53, 55.52, 37.85, and 14.30%, respectively, after 24 h. Cells expressed morphological changes like swelling, inhibition of neurite outgrowth, irregular shape, aggregation, rupture of membrane, and release of cytosolic contents after treatment with venom. Lactate dehydrogenase (LDH) level increased in 50 and 100 lg/ml as compared to control, but there was no significant increase in LDH level at a dose of 10 and 20 lg/ml. Two concentrations viz. 50 and 100 lg/ml were selected because of the profound effect of these concentrations on the cellular health and population. Treatment with these two concentrations induced reactive nitrogen intermediates and depolarization in mitochondria. While caspase-3 activity increased in a concentrationdependent manner, only 50 lg/ml was able to fragment DNA. It was interesting to note that at higher dose, i.e., 100 lg/ml, the cells were killed, supposedly by acute necrosis. DNA synthesis evidenced by bromodeoxyuridine (BrdU) incorporation was inhibited in a concentrationdependent manner. The cells without treatment incorporated BrdU with high affinity confirming their cancerous nature whereas very less incorporation was noticed in treated cells. Our results show apoptotic and antiproliferative potential of scorpion venom (O. doriae) in human neuroblastoma cells. These properties make scorpion venom a valuable therapeutic agent in cancer research.

Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells. Mol Cell Biochem. 2011 Feb;348(1-2):173-81. [Subscription required for fulltext]

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