Department of Zoology, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
J Venom Anim Toxins Incl Trop Dis. 2013 May 1;19(1):10. doi: 10.1186/1678-9199-19-10.
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.
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.
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.
据估计，海洋芋螺（属 Conus）的毒液中含有超过 100,000 种具有广泛药理和生物学作用的不同小肽。其中一些肽类已被开发为潜在的治疗药物，并作为了解神经和心血管系统生物功能的分子工具。在这项研究中，我们研究了海洋食蜗牛芋螺 Conus vexillum（从埃及的 Hurghada 和沙姆沙伊赫、红海收集）的细胞毒性和抗癌特性，并提出了可能涉及的机制。通过乳酸脱氢酶渗漏测定评估了 Conus 毒液对艾氏腹水癌（EAC）细胞的体外细胞毒性作用。
Conus 毒液处理导致细胞毒性呈浓度依赖性，如乳酸脱氢酶渗漏测定所示。通过测量注射 EAC 细胞的白化小鼠体内活性氧和氧化防御剂的水平来测量体内凋亡作用。Conus 毒液（1.25 mg/kg）在注射毒液后 3、6、9 和 12 小时诱导 EAC 细胞的几种氧化应激生物标志物（脂质过氧化、蛋白质羰基含量和活性氮中间体）显著增加（p<0.05）。Conus 毒液还显著降低了 EAC 细胞的氧化防御酶（过氧化氢酶和超氧化物歧化酶）的活性以及总抗氧化能力，这表现为还原型谷胱甘肽水平降低。
这些结果表明 C. vexillum 毒液通过诱导肿瘤细胞中的氧化应激介导机制表现出细胞毒性潜力，并表明毒液中含有具有潜在抗癌活性的新型分子。
