Department of Biological Sciences, School of Science and Technology, Sunway University, Bandar Sunway, Selangor, Malaysia.
Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, University City, Sharjah, United Arab Emirates.
Anticancer Agents Med Chem. 2020;20(13):1558-1570. doi: 10.2174/1871520620666200504103056.
Cancer contributes to significant morbidity and mortality despite advances in treatment and supportive care. There is a need for the identification of effective anticancer agents. Reptiles such as tortoise, python, and water monitor lizards are exposed to heavy metals, tolerate high levels of radiation, feed on rotten/germ-infested feed, thrive in unsanitary habitat and yet have prolonged lifespans. Such species are rarely reported to develop cancer, suggesting the presence of anticancer molecules/mechanisms.
Here, we tested effects from sera of Asian water monitor lizard (Varanus salvator), python (Malayopython reticulatus) and tortoise (Cuora kamaroma amboinensis) against cancer cells. Sera were collected and cytotoxicity assays were performed using prostate cancer cells (PC3), Henrietta Lacks cervical adenocarcinoma cells (HeLa) and human breast adenocarcinoma cells (MCF7), as well as human keratinized skin cells (Hacat), by measuring lactate dehydrogenase release as an indicator for cell death. Growth inhibition assays were performed to determine the effects on cancer cell proliferation. Liquid chromatography mass spectrometry was performed for molecular identification.
The findings revealed that reptilian sera, but not bovine serum, abolished viability of Hela, PC3 and MCF7 cells. Samples were subjected to liquid chromatography mass spectrometry, which detected 57 molecules from V. salvator, 81 molecules from Malayopython reticulatus and 33 molecules from C. kamaroma amboinensis and putatively identified 9 molecules from V. salvator, 20 molecules from Malayopython reticulatus and 9 molecules from C. kamaroma amboinensis when matched against METLIN database. Based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition, 123 potential Anticancer Peptides (ACPs) were identified from 883 peptides from V. salvator, 306 potential ACPs from 1074 peptides from Malayopython reticulatus and 235 potential ACPs from 885 peptides from C. kamaroma amboinensis.
To our knowledge, for the first time, we reported comprehensive analyses of selected reptiles' sera using liquid chromatography mass spectrometry, leading to the identification of potentially novel anticancer agents. We hope that the discovery of molecules from these animals will pave the way for the rational development of new anticancer agents.
尽管治疗和支持性护理取得了进展，但癌症仍导致了大量的发病率和死亡率。因此，我们需要寻找有效的抗癌药物。乌龟、蟒蛇和水巨蜥等爬行动物长期暴露于重金属环境中，能承受高强度的辐射，以腐烂/受感染的饲料为食，生活在不卫生的环境中，但它们的寿命却很长。这些物种很少被报道患有癌症，这表明它们可能存在抗癌分子/机制。
在这里，我们测试了亚洲水巨蜥（Varanus salvator）、蟒蛇（Malayopython reticulatus）和乌龟（Cuora kamaroma amboinensis）的血清对癌细胞的影响。收集血清，并使用前列腺癌细胞（PC3）、亨氏宫颈癌腺癌细胞（HeLa）和人乳腺癌腺癌细胞（MCF7）以及人角化皮肤细胞（Hacat）进行细胞毒性测定，通过测量乳酸脱氢酶释放作为细胞死亡的指标来检测血清对癌细胞的杀伤作用。通过生长抑制试验来确定血清对癌细胞增殖的影响。使用液相色谱质谱法进行分子鉴定。
研究结果表明，爬行动物血清而非牛血清能消除 HeLa、PC3 和 MCF7 细胞的活力。对这些样本进行液相色谱质谱分析，从 V. salvator 中检测到 57 种分子，从 Malayopython reticulatus 中检测到 81 种分子，从 C. kamaroma amboinensis 中检测到 33 种分子，并与 METLIN 数据库进行匹配，鉴定出 V. salvator 中的 9 种分子、Malayopython reticulatus 中的 20 种分子和 C. kamaroma amboinensis 中的 9 种分子。基于肽的氨基酸组成、二元分布、二肽组成和伪氨基酸组成，从 V. salvator 的 883 种肽中鉴定出 123 种潜在的抗癌肽（ACP），从 Malayopython reticulatus 的 1074 种肽中鉴定出 306 种潜在的 ACP，从 C. kamaroma amboinensis 的 885 种肽中鉴定出 235 种潜在的 ACP。
据我们所知，这是首次使用液相色谱质谱法对选定的爬行动物血清进行全面分析，从而鉴定出潜在的新型抗癌药物。我们希望这些动物的分子发现能为合理开发新的抗癌药物铺平道路。
