Background Cancer remains a global threat resulting in significant morbidity and mortality despite advances in therapeutic interventions, suggesting urgency for identification of anticancer agents. Crocodiles thrive in polluted habitat, feed on germ-infested meat, are exposed to carcinogenic heavy metals, are the very few species to survive the catastrophic Cretaceous–Paleogene extinction event, yet have a prolonged lifespan and rarely been reported to develop cancer. Therefore, we hypothesised that animals living in polluted environments such as crocodiles possess anticancer molecules/mechanisms. Methods Crocodylus porosus was procured, blood collected, dissected and lysates prepared from internal organs. Organ lysates and sera were tested for growth inhibition, cytotoxic effects and cell survival against HeLa, PC3 and MCF7 cells and subjected to liquid chromatography mass spectrometry. RNA transcriptome analysis and differential gene analysis were performed using Galaxy Bioinformatics. Results Sera exhibited potent growth inhibition and cytotoxic effects against cancer cells. 80 molecules were detected from C. porosus and 19 molecules were putatively identified. Additionally, more than 100 potential anticancer peptides were identified from sera using bioinformatics based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition. Following transcriptome analysis, 14 genes in treated HeLa cells, 51 genes in treated MCF7 cells and 2 genes in treated PC3 cells, were found to be expressed, compared with untreated controls. Conclusion Animals residing in polluted milieus are an unexploited source for prospective pharmaceutical drugs, and could lead to identification of novel antitumour compound(s) and/or further understanding of the mechanisms of cancer resistance.

中文翻译：

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Crocodylus porosus：抗癌分子的潜在来源

背景 尽管治疗干预取得了进展，但癌症仍然是一个全球性威胁，导致显着的发病率和死亡率，这表明鉴定抗癌剂的紧迫性。鳄鱼在受污染的栖息地茁壮成长，以受细菌感染的肉类为食，暴露于致癌重金属中，是极少数在白垩纪-古近纪灾难性灭绝事件中幸存下来的物种，但寿命却很长，很少有报道患上癌症。因此，我们假设生活在鳄鱼等污染环境中的动物具有抗癌分子/机制。方法 获取孔鳄，采血，解剖，内脏制备裂解液。检测器官裂解物和血清对 HeLa 的生长抑制、细胞毒作用和细胞存活，PC3 和 MCF7 细胞并进行液相色谱质谱分析。使用 Galaxy Bioinformatics 进行 RNA 转录组分析和差异基因分析。结果血清对癌细胞表现出有效的生长抑制和细胞毒作用。从 C. porosus 中检测到 80 个分子，推定鉴定了 19 个分子。此外，利用基于肽氨基酸组成、二元谱、二肽组成和假氨基酸组成的生物信息学从血清中鉴定出 100 多种潜在的抗癌肽。在转录组分析之后，与未处理的对照相比，发现处理过的 HeLa 细胞中的 14 个基因、处理过的 MCF7 细胞中的 51 个基因和处理过的 PC3 细胞中的 2 个基因被表达。