The Proteome of African Spitting and Non-Spitting Cobra Venoms and Cytotoxicity Against Pancreatic Cancer Cells.

IF 2.8 4区 医学 Q3 TOXICOLOGY
Benedict C Offor, Beric Muller, Lesetja R Motadi, Lizelle A Piater
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引用次数: 0

Abstract

African cobra (Naja spp.) venom contains toxins dominated by proteins and peptides with inter- and intra-specific variations. There are several FDA-approved drugs from snake venom toxins from other regions, including South America and Asia. Profiling the proteomes of medically important African cobra venoms from different locations will aid in developing more effective anticancer agents. The venoms of spitting cobras (Naja pallida and Naja nigricincta woodi) and non-spitting cobras of the Uraeus subgenus (Naja anchietae, Naja annulifera, and Naja nivea) were fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Using label-free LC-MS/MS, the venom toxins were identified and grouped into families based on their relative abundance. Venom cytotoxicity of both crude and fractionated samples was tested in pancreatic carcinoma cell lines (MIA PaCa-2) using the Alamar Blue assay. Cell viability analysis revealed a cytotoxic effect of spitting cobra venoms against MIA PaCa-2 cell lines compared to normal MRC-5 cells. Conversely, venoms of non-spitting cobras showed no cytotoxic activity against MIA PaCa-2 cells. Selected RP-HPLC venom fractions from the spitting cobras revealed that N. pallida Fraction 6 and N. n. woodi Fraction 9 at a minimal level were cytotoxic against MIA PaCa-2 cells. LC-MS/MS data showed that while N. pallida Fraction 6 was dominated by basic phospholipase 2 CM-III and Cytotoxin 2, N. n. woodi Fraction 9 was dominated by basic phospholipase 2 CM-III, basic phospholipase 2 CM-II and Cytotoxin 3. These fractions will be purified and studied to determine the mechanisms behind the underlying cytotoxicity against MIA PaCa-2 cells.

非洲吐痰和不吐痰眼镜蛇毒液的蛋白质组学及其对胰腺癌细胞的细胞毒性。
非洲眼镜蛇(眼镜蛇属)的毒液含有由蛋白质和多肽主导的毒素,具有种间和种内变异。美国食品药品监督管理局(fda)已经批准了几种从南美和亚洲等其他地区的蛇毒毒素中提取的药物。对来自不同地点的具有重要医学意义的非洲眼镜蛇毒液的蛋白质组进行分析,将有助于开发更有效的抗癌药物。采用反相高效液相色谱法(RP-HPLC)分离了吐舌眼镜蛇(Naja pallida和Naja nigricincta woodi)和不吐舌眼镜蛇(Naja anchietae, Naja anniclifera和Naja nivea)的毒液。采用无标签LC-MS/MS技术,根据其相对丰度对毒液毒素进行鉴定和分类。用Alamar Blue法在胰腺癌细胞系(MIA PaCa-2)中测试了粗样品和分离样品的毒液细胞毒性。细胞活力分析显示,与正常MRC-5细胞相比,吐蛇毒液对MIA PaCa-2细胞系具有细胞毒性作用。相反,不吐痰的眼镜蛇的毒液对MIA PaCa-2细胞没有细胞毒性活性。经RP-HPLC筛选,结果表明,nn . pallida馏分6和nn . woodi馏分9对MIA PaCa-2细胞具有一定的细胞毒性。LC-MS/MS数据显示,褐藻第6部分以碱性磷脂酶2cm - iii和细胞毒素2为主,而木桐第9部分以碱性磷脂酶2cm - iii、碱性磷脂酶2cm - ii和细胞毒素3为主。这些部分将被纯化和研究,以确定对MIA PaCa-2细胞潜在细胞毒性背后的机制。
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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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