Abstract
Research on animal toxins have shown toxicity potential on cancerous cell and tissues in the cultures. Conotoxins obtained from marine cone snails show the highest toxicity potential, so that several human deaths have been attributed to this species of snail. These toxins have proven to be valuable agents to inhibit enzymes, channels and proteins, in the nervous systems of humans. We have studied the effects of Conus textile crude venom on U87MG human glioma cells and their mitochondria as main inducers of apoptosis and human embryonic kidney 293 cells (HEK293) as non-cancerous normal control cells. Cellular toxicity assessments including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and measurement of caspase-3 activation as well as mitochondrial toxicity assays including measurement of the activity of succinate dehydrogenase (SDH) enzyme, mitochondrial swelling, reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were performed in U87MG human glioma cells and HEK293 cells (as non-cancerous normal cells). The results illustrated the significant cytotoxic effect of Conus textile crude venom on U87MG human glioma cells, that inhibits 50% (IC50=10µg/mL) of the cell growth after 12 h of exposure. Viability measurement showed which the Conus textile crude venom is selectively cytotoxic to U87MG human glioma cells, and induced activation of caspase-3 and induction of cell apoptosis via through mitochondrial signaling. Conus textile crude venom also selectively increased mitochondria swelling, ROS formation, cytochrome c release and MMP decrease in cancerous mitochondria but not normal mitochondria. Conclusion; Based on the obtained results from this investigation, it is concluded that the Conus textile crude venom contains promising natural compounds to fight U87MG human glioma cells through activation of apoptosis intrinsic pathways.
Highlights
Animal toxins are made of types of peptides and proteins well-tuned during millions of years of evolution (Escoubas and King, 2009)
We have studied the effects of Conus textile crude venom on U87MG human glioma cells and their mitochondria as main inducers of apoptosis and human embryonic kidney 293 cells (HEK293) as non-cancerous normal control cells
Cell Viability Assay For determination of cytotoxic effect of Conus textile crude venom on U87MG human glioma cells and human embryonic kidney 293 cells we used MTT assay
Summary
Animal toxins are made of types of peptides and proteins well-tuned during millions of years of evolution (Escoubas and King, 2009) These venoms target various enzymes, receptors, and ion channels with great potency and sometimes good selectivity, it is led to more attention to more research their physiological and pharmacological attributes (Escoubas and King, 2009). Animal toxins display higher potency and selectivity compared to drugs for pharmacological application, they still face many challenges, such as the poor oral bioavailability, lack of membrane permeability and short circulating half-life (Chen et al, 2018) Marine cone snails such as Conus textile prepare one of the highest toxin varieties between toxic animals. Conclusion; Based on the obtained results from this investigation, it is concluded that the Conus textile crude venom contains promising natural compounds to fight U87MG human glioma cells through activation of apoptosis intrinsic pathways
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