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.
Highlights
According to the reports and statistics from the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO), cancer has become the leading cause of deaths worldwide (7.6, 8.2 million deaths in 2008 and 2012, respectively) (Jemal et al 2011; Ferlay et al 2013)
In vitro cytotoxic effect of A. amoreuxi venom The short-term in vitro cytotoxicity study showed that the IC50 value of A. amoreuxi venom on MCF-7 cell line was 0.61 μg/ml
In an attempt to check whether the death of MCF-7 cells that occurred as a consequence of A. amoreuxi venom treatment was due to apoptosis, DNA fragmentation analysis was performed
Summary
According to the reports and statistics from the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO), cancer has become the leading cause of deaths worldwide (7.6, 8.2 million deaths in 2008 and 2012, respectively) (Jemal et al 2011; Ferlay et al 2013). Disulfide-bridged peptides and non-disulfidebridged peptides constitute the major groups of scorpion venom and many of them have been characterized with analgesic, anti-epileptic, hemolytic, anti-thrombotic, anti-inflammatory, antimicrobial and anticancer activities (Yu et al 1992; Wang et al 2001; Zeng et al 2005; Song et al 2005; Shao et al 2007; Mamelak 2011; Harrison et al 2014, 2016; Almaaytah and Albalas 2014; Abdel-Rahman et al 2016). Venom from the Buthidae scorpions Androctonus bicolor, Androctonus crassicauda, and Leiurus quinquestriatus (collected from Saudi Arabia) revealed strong anticancer activity on colorectal and breast cancer cell lines (HCT-116 and MDA-MB-231, respectively) through decreasing cell motility and colony formation of cancer cells (Al-Asmari et al 2016)
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