Shekarabi Seyed Mahdi, Parsian Hadi, Pooshang Bagheri Kamran, Shahbazzadeh Delavar
Biotechnology Research Center, Medical Biotechnology Department, Venom and Biotherapeutics Molecules Lab., Pasteur Institute of Iran, Tehran, Iran.
Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran.
Iran J Pharm Res. 2022 Dec 20;21(1):e129616. doi: 10.5812/ijpr-129616. eCollection 2022 Dec.
The discovery of novel anti-cancer agents from natural resources is highly necessary. Concerning the above problem, the purpose of this study was to discover an anti-cancer compound from Caspian cobra venom. Fractionation of Caspian cobra venom was performed by gel filtration and IEX chromatography. The results showed an anti-cancer protein nominated as Oxilipin. Activity and toxicity of Oxilipin were studied on the colon SW480 cancer cell line using MTT, LDH release, PI staining, morphological cell analysis, hemolysis, and anti-proliferation assays. Oxilipin, an 11kDa protein purified from the venom of the Caspian cobra. LC/MS/MS analysis of obtained protein showed homology with Phospholipase A2 from . 40 µg/ml of Oxilipin can induce an apoptotic effect in SW480 cell line up to 90%; meanwhile, this amount can induce only one-third of cytotoxicity on a normal cell. In this study, Iranian cobra venom was found to have cytotoxic effects on SW480 colon cancer tumor cells, with the least cytotoxicity on normal cells on HEK-293. Given that Oxilipin has slight toxicity on normal cells, it can be hypothesized that the obtained peptide can be considered as a drug lead in an animal model study of colon cancer.
从自然资源中发现新型抗癌药物非常必要。针对上述问题,本研究的目的是从里海眼镜蛇毒液中发现一种抗癌化合物。通过凝胶过滤和离子交换色谱法对里海眼镜蛇毒液进行分离。结果显示一种名为氧化脂质的抗癌蛋白。使用MTT、LDH释放、PI染色、细胞形态分析、溶血和抗增殖试验,对结肠SW480癌细胞系研究了氧化脂质的活性和毒性。氧化脂质是一种从里海眼镜蛇毒液中纯化得到的11kDa蛋白。对所得蛋白的LC/MS/MS分析显示与来自[具体来源未给出]的磷脂酶A2具有同源性。40µg/ml的氧化脂质可在SW480细胞系中诱导高达90%的凋亡效应;与此同时,该剂量对正常细胞仅诱导三分之一的细胞毒性。在本研究中,发现伊朗眼镜蛇毒液对SW480结肠癌细胞具有细胞毒性作用,对HEK - 293正常细胞的细胞毒性最小。鉴于氧化脂质对正常细胞毒性轻微,可以推测所获得的肽在结肠癌动物模型研究中可被视为一种药物先导物。