Abstract
BackgroundIt is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich’s ascites carcinoma (EAC) cells.ResultsConus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione.ConclusionsThese results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity.
Highlights
It is estimated that venoms of marine cone snails contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions
In vitro cytotoxicity of Conus venom The membrane integrity of Ehrlich’s ascites carcinoma (EAC) cells treated with C. vexillum venom, obtained from either Hurgada or Sharm El-Shaikh, was evaluated by measuring the levels of Lactate dehydrogenase (LDH) activity in cell culture supernatants
LDH levels in cells incubated with Conus venom for one hour from each location showed a significant (p < 0.05) dosedependent increase in comparison to the levels in vehicle-treated cells (Table 1)
Summary
It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. Venoms of animal species (such as snakes, scorpions, spiders and cone snails) are a combination of unique bioactive molecules that display a plethora of molecular targets and functions. Some of these molecules are currently being developed as candidate or to provide a critical template for the design of others [2]. Development of alternative anticancer drugs with minimal side-effects is urgently required
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