ABSTRACT
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. 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 Ehrlichs ascites carcinoma (EAC) cells. Results Conus 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.Conclusions These 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.
Subject(s)
Animals , Mice , Carcinoma/complications , Mollusk Venoms , Poisons/toxicity , Mice/physiology , SnailsABSTRACT
Background: 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. 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. Results: Conus 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. Conclusions: These 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.(AU)
Subject(s)
Animals , Male , Mice , Carcinoma, Ehrlich Tumor , Oxidative Stress , Conus Snail/cytology , Mollusk Venoms/toxicity , Mollusk Venoms/pharmacology , In Vitro Techniques , Apoptosis/physiology , Egypt , Antineoplastic Agents/pharmacologyABSTRACT
The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46 percent) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.
O presente estudo foi realizado para verificar o efeito do extrato cru de folhas de Cleome droserifolia (CD) em camundongos experimentalmente infectados com Schistosoma mansoni. Em dois grupos de camundongos mostrando infecção patente por S. mansoni, um deles foi tratado diariamente com extrato alcoólico de folhas de CD (0.31g kg-1 por peso corporal, i.p.) por 21 dias. A atividade esquistossomicida do extrato de CD foi avaliada, três semanas após o tratamento, em alguns aspectos parasitológicos e histopatológicos incluindo carga parasitária, padrão de oograma, eliminação fecal de ovos e formação de granuloma. Além disto, níveis séricos de hormônio tireoideano (tri-iodotironina: T3 e tetra-iodotironina: T4), conteúdo sérico total de proteínas e glutatione hepático reduzido (GSH) foram avaliados. Tratamento usando extrato de CD resultou em fraca redução da carga de vermes (32,46 por cento) e afetou a viabilidade de ovos maduros ou não, como indicado pelo aumento na porcentagem de ovos mortos e o descrécimo na porcentagem de ovos viáveis. Além disso, uma semana após o tratamento, a eliminação de ovos foi observada nas fezes do grupo infectado-tratado que foi baixa comparada ao grupo infectado. Houve efeito supressivo do extrato sobre a formação de granuloma que poderia ser devido ao efeito antioxidante do extrato. Estes dados são confirmados pelo aumento do GSH hepático, soro total de proteínas e níveis dos hormônios tireoideanos no grupo infecto-tratado quando comparado com o grupo infectado. O tratamento aumentou significativamente as frações beta-globulina da proteína. Baseado nestas afirmativas o extrato de CD tem efeitos benéficos sobre o nível dos hormônios tireoideanos e da atividade anti-esquistossomica. Os efeitos benéficos do extrato de CD poderiam estar relacionados com seu efeito direto sobre o parasita, e secundariamente por seus efeitos na capacidade anti-oxidante do hospedeiro. O presente trabalho poderia enfatizar o(s) mecanismo(s) preciso(s) desta proteção do extrato de CD.