A. crassicauda, M. eupeus and H. lepturus scorpion venoms initiate a strong in vivo anticancer immune response in CT26-tumor mice model

Abstract

In the present in vivo study the anticancer efficacy of the venoms from Androctonus crassicauda, Messobuthus eupeus and Hemiscorpius lepturus scorpions was investigated. In addition, we attempted to clarify whether the immune system is involved in this activity. Initially, the LD50 of the venoms from these scorpions were determined and their 0.1 and 0.2 LD50 were calculated. The toxicity of 0.1 and 0.2 LD50 was tested on healthy mice by daily SC administration of these venoms for 12 consecutive days. CT26 cells were inoculated by SC route in BALB/c mice to establish a sold tumor, and ten days later, the mice were treated with 0.1 and 0.2 LD50 doses of the venoms on daily basis for 12 consecutive days. The tumor volume was measured every 4 days. At day 13, the tumors from untreated-control and venom-treated groups were removed, weighed, and assessed by histopathological and immunohistochemical techniques. In addition, the levels of mRNA expression of IL-12, IFN-γ and IL-1β were measured by real-time PCR. All the venoms induced anticancer effects as evidenced by significant inhibition in tumor growth; significant increases in inflammatory and CD+-T cells and expression of mRNA IL-12 and IFN-γ in tumor microenvironment of venom-treated as compared to untreated-control. These findings demonstrated, for the first time, that sub-lethal doses of the venoms from these scorpions induce their in vivo anticancer effects by stimulating the immune system. Further studies, specifically designed to identify these active constituents are recommended.