Egyptian Cobra Venom and Honey Bee Venom Treatment Ameliorated Levels of Neuropilin 1, Angiopoietin 2, and DNA Topoisomerase II Binding Protein 1 in Induced Hepatocellular Carcinoma in Albino Rats.

内容摘要

Hepatocellular carcinoma (HCC) is a critical health problem that is classified as the fifth most prevalent malignancy in the world. Our study aimed to investigate the anti-tumor activity of the Egyptian cobra venom and honey bee venom in the treatment of DENA-induced HCC in rats compared to the chemotherapeutic drug cisplatin. 70 male adult albino rats were randomly placed into seven groups. Group 1 served as a negative control. Group 2 received 0.1 LD50 snake venom (SV). Group 3 received 0.1 LD50 bee venom (BV). While the other four groups received diethylnitrosamine (DENA) to induce HCC, they were subsequently divided as follows: Group 4 served as a positive control group (HCC), and the other three remaining groups represented the treated groups. Group 5: snake venom-treated group (HCC+SV). Group 6: bee venom-treated group (HCC+BV). Group 7: Cisplatin-treated group (HCC+CIS). DENA induced HCC, as proved by a significantly high increase in AST, ALT, GGT, and ALP activities and a decrease in total protein and albumin contents. Also, significantly elevated levels of urea, creatinine, proinflammatory cytokine (IL-1β), and tumor markers (NRP1, ANG2, TOPBP1) in comparison to the negative control group. Treatment of HCC rats using snake venom, bee venom, and cisplatin revealed a significant decrease in liver enzymes and tumor markers. The venoms showed a potent synergistic anti-tumor effect by significantly upregulating the expression of pro-apoptotic gene Caspase 3 and downregulating the expression of the anti-apoptotic gene (Bcl-2) in comparison to the positive control HCC group. Our findings were confirmed by histological analysis and immunohistochemical Caspase-3 expression. Both snake venom and bee venom have anti-inflammatory, apoptotic, and anticancer effects against induced HCC. However, the use of BV is more effective and safer than SV. Egyptian cobra venom and honey bee venom may serve as an apoptotic stimulator, and can be considered as novel potential therapeutic against HCC.