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

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.

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti‐Inflammatory Agents

“…[40,41] Ibuprofen can be prescribed for various diseases, like arthritis, osteoarthritis, and musculoskeletal disorders. [42] While the effects of NSAIDs include the inhibition of cyclooxygenase (COX) enzyme activity; [43][44][45] it has been demonstrated that inhibition of COX-2 has serious side effects such as gastrointestinal injury, as well as kidney and liver damage and cardiac arrest. [46,47] In addition, treatments of bacterial infections with ibuprofen speed the recovery process from vaginal infections, cellulitis, or acne.…”

A Review of Rattlesnake Venoms

“…Nerve growth factor (NGF) is among the least abundant toxins in snake venom [ 191 , 192 , 193 , 194 , 195 , 196 ]. Nevertheless, snake venom is considered a rich active source of this peptide [ 197 , 198 ].…”

“…First is the tropomyosin kinase receptor A (TrkA), with high and specific affinity [ 194 , 208 ], triggers the MAPK, ERK, and PI3K/AKT cytosolic/endosomal pathways [ 197 , 208 ], leading to proliferation arrest and the induction of differentiation in neuronal cells [ 207 ]. Second is the p75 pan-NT receptor (p75NTR) [ 194 , 197 ], with similar affinity but not specificity, is linked to cell apoptosis and growth arrest via the MAPK c-Jun N-terminal kinase pathways [ 209 ]. Interestingly, both NGF receptors have been observed to be expressed in tumors in the nervous system and are especially prevalent in breast cancer [ 198 ].…”

“…Interestingly, both NGF receptors have been observed to be expressed in tumors in the nervous system and are especially prevalent in breast cancer [ 198 ]. NGF can promote or suppress tumor growth depending on tumor types [ 194 , 203 ], with prominent examples of NGFs from cobra venom inhibiting the growth of Ehrlich’s adenocarcinoma in vivo [ 194 , 198 , 210 ], but proliferative activity on breast cancer cell line MCF-7 [ 203 , 210 , 211 ]. Lately, NGF has been found to have a link to human diseases, including Alzheimer’s disease [ 200 , 212 ].…”

Toxins in Drug Discovery and Pharmacology

“…This work suggests that the antitumor effect of nerve growth factor in vivo depends critically on the normal status of the immune system. The nerve growth factor antitumor mechanism may cause an increase in lymphocytic infiltration in the tumor, a rise in the levels of IL-1β and TNF-α in the serum of tumor-bearing mice, and an increase in aerobic glycolysis [ 11 ]. Sales et al [ 12 ] questioned whether inhibitors of snake venom phospholipases A2 can lead to new insights into anti-inflammatory therapy in humans.…”