In vitro and in vivo antitumor effects of the Egyptian scorpion Androctonus amoreuxi venom in an Ehrlich ascites tumor model

Abstract

Scorpion venom is a highly complex mixture of about 100–700 different components, where peptides are the major constituents with various biological and pharmacological properties including anticancer activities. In this study, anticancer efficacy of the venom of the Egyptian scorpion Androctonus amoreuxi has been evaluated. In vitro, the human breast cancer MCF-7 cell line was treated with the venom and the IC50 was estimated. In vivo studies, Ehrlich ascites carcinoma (EAC) cells were inoculated into CD-1 mice intraperitoneally to form liquid tumor or subcutaneously to form solid tumor and then treated with intraperitoneal injection with venom (0.22 mg/kg) every other day. The total tumor cells in the ascitic fluid and the size of the solid tumor were assessed after 14 and 30 days, respectively. In addition, the mean survival time (MST), body weight, tumor volume, PCV, viability of tumor cells, CBC, AST, ALP, creatinine, oxidative stress biomarkers (GSH, MDA, PCC), tumor marker Ki67, growth factor VEGF and caspase-3 were measured in normal control, EAC control and venom-treated groups (n = 6). Treatment with venom induced anti-tumor effects against liquid and in solid tumors as indicated by a significant (P < 0.05) reduction in tumor volume/size, count of viable EAC cells, expression of Ki67 and VEGF as well as by remarkable increases in MST and caspase-3 expression as compared to non-treated group. Interestingly, the venom restored the altered hematological and biochemical parameters of tumor-bearing animals and significantly increased their life span. These data indicate to (1) the cytotoxic potential effects of A. amoreuxi on tumor cells via anti-proliferative, apoptotic and anti-angiogenic activities; (2) opening a new avenue for further studies on the anti-cancer effects of this agent.

Vanadium(III)-l-cysteine enhances the sensitivity of murine breast adenocarcinoma cells to cyclophosphamide by promoting apoptosis and blocking angiogenesis

“…In this study, VC-III itself showed promising chemopotentiating efficacy in tumor-bearing mice as evident from suppression of tumor burden and prolongation of host survivability, which is one of the important criteria to evaluate the potency of anticancer drugs. 16 VC-III in combination with cyclophosphamide substantially enhanced the life span of tumor-bearing mice compared to the cyclophosphamide monotherapy, which reflects the potential advantage of this combination in chemotherapy. Although the precise molecular mechanisms by which VC-III modulates cyclophosphamide therapy are not fully understood at this moment, a number of factors which could have an impact are discussed herein.…”

“…According to the criteria of National Cancer Institute (NCI), T/C > 125% and ILS > 25% indicate that the drug has a significant antitumor activity. 16 Detection of apoptosis by Annexin V positivity Double staining for Annexin V-FITC and PI was performed using FITC Annexin V Apoptosis Detection Kit I (BD Pharmingen) according to the manufacturer's protocol. Briefly, tumor cells were collected in PBS, centrifuged, and washed.…”

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

“…Akef, Kotb, Abo‐Elmatty, and Salem (2017) reported anticancer characteristics of Androctonus amoreuxi against the PC‐3 cell line (human prostate adenocarcinoma), exhibiting 93% cancer cells death within 24 h at a concentration of 5.58 μg/mL. A. amoreuxi , at a concentration of 0.61 μg/mL showed anticancer activity against the MCF‐7 cell line (human breast adenocarcinoma) with 83.7% cancer cells death within 24 h (Salem, Shoukry, Teleb, Abdel‐Daim, & Abdel‐Rahman, 2016). A. crassicauda , at a concentration of 100 μg/mL had anticancer activity against the HCT‐116 cell line (human colorectal carcinoma), which showed 80% of cancer cells death (Al‐Asmari et al, 2016).…”

“…A. crassicauda , at a concentration of 100 μg/mL had anticancer activity against the HCT‐116 cell line (human colorectal carcinoma), which showed 80% of cancer cells death (Al‐Asmari et al, 2016). In another study, A. crassicauda at 80 μg/mL, had an anticancer trait against the MDA‐MB‐231 cell line (human breast adenocarcinoma), with 24% of cancer cells death within 24 h (Salem et al, 2016). Díaz‐García et al (2013) reported anticancer attributes of Rhopalurus junceus (1 mg/mL) against the MDA‐MB‐468 cell line (human breast adenocarcinoma), which showed 64.5% of cancer cells death after 72 h. Al‐Asmari et al (2016) demonstrated tumoricidal property of Androctonus bicolor (100 μg/mL) in the MDA‐MB‐231 cell line, with 63% cancer cell death after 24 h. Similarly, Leiurus quinquestriatus showed 63% cancer cells death against the MDA‐MB‐231 after 24 h (Al‐Asmari et al, 2016).…”

Antitumor efficacy of the Egyptian Scorpion Venom Androctonus Australis: in vitro and in vivo study

“…Recently, scorpion venoms obtained from various scorpion species (L. quinquestriatus, A. crassicauda, and A. amouroxi) revealed potential anticancer effects using in vitro and in vivo approaches. The venoms induced cytotoxicity, elevated the reactive oxygen species, and also enhanced apoptotic pathways in these cancer cell lines (Salem et al 2016;Al-Asmari et al 2018). Also, from the scorpion of A. australis (one of the most common species in North Africa), the venom fraction F3 induced apoptosis in human lung cancer cell line (NCI-H358) via generation of reactive oxygen and nitrogen species resulted in mitochondrial malfunction (Béchohra et al 2016).…”