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Toxins 2017, 9(9), 274; doi:10.3390/toxins9090274

Cobra Venom Factor and Ketoprofen Abolish the Antitumor Effect of Nerve Growth Factor from Cobra Venom

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia
2
Institute of Physiology, National Academy of Sciences of Belarus, ul. Akademicheskaya, 28, Minsk 220072, Belarus
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Steve Peigneur
Received: 17 August 2017 / Revised: 1 September 2017 / Accepted: 2 September 2017 / Published: 6 September 2017
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
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Abstract

We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor NGF effect, as well as on NGF-induced changes in EAC histological patterns, the activity of lactate and succinate dehydrogenases in tumor cells and the serum level of some cytokines. NGF, CVF and ketoprofen reduced the tumor volume by approximately 72%, 68% and 30%, respectively. The antitumor effect of NGF was accompanied by an increase in the lymphocytic infiltration of the tumor tissue, the level of interleukin 1β and tumor necrosis factor α in the serum, as well as the activity of lactate and succinate dehydrogenases in tumor cells. Simultaneous administration of NGF with either CVF or ketoprofen abolished the antitumor effect and reduced all other effects of NGF, whereas NGF itself significantly decreased the antitumor action of both CVF and ketoprofen. Thus, the antitumor effect of NGF critically depended on the status of the immune system and was abolished by the disturbance of the complement system; the disturbance of the inflammatory response canceled the antitumor effect as well. View Full-Text
Keywords: Ehrlich carcinoma; immune system; nerve growth factor; cobra venom; cobra venom factor; ketoprofen Ehrlich carcinoma; immune system; nerve growth factor; cobra venom; cobra venom factor; ketoprofen
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MDPI and ACS Style

Osipov, A.V.; Terpinskaya, T.I.; Kuznetsova, T.E.; Ryzhkovskaya, E.L.; Lukashevich, V.S.; Rudnichenko, J.A.; Ulashchyk, V.S.; Starkov, V.G.; Utkin, Y.N. Cobra Venom Factor and Ketoprofen Abolish the Antitumor Effect of Nerve Growth Factor from Cobra Venom. Toxins 2017, 9, 274.

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