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

Toxins (Basel). 2017 Sep 6;9(9):274. doi: 10.3390/toxins9090274.

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.

Keywords: Ehrlich carcinoma; cobra venom; cobra venom factor; immune system; ketoprofen; nerve growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Ehrlich Tumor / blood
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Carcinoma, Ehrlich Tumor / pathology
  • Cytokines / blood
  • Elapid Venoms / chemistry*
  • Elapid Venoms / pharmacology
  • Elapid Venoms / therapeutic use
  • Female
  • Glycolysis / drug effects
  • Ketoprofen / pharmacology
  • Ketoprofen / therapeutic use*
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Nerve Growth Factor / pharmacology
  • Nerve Growth Factor / therapeutic use*
  • Succinate Dehydrogenase / metabolism
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Cytokines
  • Elapid Venoms
  • cobra venom factor
  • Nerve Growth Factor
  • Ketoprofen
  • L-Lactate Dehydrogenase
  • Succinate Dehydrogenase