Al-Hassan Jassim M, Afzal Mohammad, Oommen Sosamma, Liu Yuan Fang, Pace-Asciak Cecil
Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait, Kuwait.
Program in Translational Medicine, Peter Gilgan Centre for Research and Learning (PGCRL), The Hospital for Sick Children, Toronto, ON, Canada.
Front Pharmacol. 2022 Oct 14;13:1001067. doi: 10.3389/fphar.2022.1001067. eCollection 2022.
The edible catfish (Valenciennes) elaborates a proteinaceous gel-like material through its epidermis when threatened or injured. Our on-going studies on this gel have shown it to be a complex mixture of several biologically active molecules. Anti-cancer studies on lipid fractions isolated from the gel-like materials showed them to be active against several cancer cell lines. This prompted us to investigate further the lipid composition of the catfish epidermal gel secretions (EGS). Analysis of the lipid fraction of EGS resulted in identification of 12 oxysterols including cholesterol and 2 deoxygenated steroids i.e., 7α-hydroxy cholesterol, 7β-hydroxycholesterol, 5,6 epoxycholesterol, 3β-hydroxycholest-5-ene-7-one and cholesta-3,5-dien-7-one. Progesterone, cholest-3,5-diene, cholesta-2,4-diene, cholest-3,5,6-triol and 4-cholesten-3-one were found as minor components, and were identified through their MS, HNMR and FTIR spectral data and were compared with those of the standards. Cholest-3,6-dione, cholesta-4,6-diene-3-one, cholesta-2,4-diene, and cholesta-5,20(22)-dien-3-ol were found only in trace amounts and were identified by GC/MS/MS spectral data. Since cholesterol is the major component of EGS, the identified oxysterols (OS) are presumably cholesterol oxidation products. Many of the identified OS are known important biological molecules that play vital physiological role in the producer and recipient organisms. We report herein the effects of these sterols on three human cancer cell lines , i.e., K-562 (CML cell line), MDA MB-231 (estrogen positive breast cancer cell line) and MCF-7 (estrogen negative breast cancer cell line). Interestingly significant ( < 0.05) dose differences were observed between tested OS on cell types used. The presence of these sterols in EGS may help explain some aspects of the physiological activities of fraction B (FB) prepared from EGS, such as enhanced wound and diabetic ulcer healing, anti-inflammatory action and cytotoxic activities reported in our previous studies. The anti-proliferative actions of some of these oxysterols especially the cholesterol 3,5,6-triol (#5) as established on selected cancer cell lines in this study support our previous studies and make them candidates for research for human application.
可食用鲶鱼（瓦伦西恩斯鲶）在受到威胁或受伤时会通过其表皮分泌出一种蛋白质类凝胶状物质。我们对这种凝胶的持续研究表明，它是几种生物活性分子的复杂混合物。对从凝胶状物质中分离出的脂质部分进行的抗癌研究表明，它们对几种癌细胞系具有活性。这促使我们进一步研究鲶鱼表皮凝胶分泌物（EGS）的脂质组成。对EGS脂质部分的分析导致鉴定出12种氧甾醇，包括胆固醇和2种脱氧类固醇，即7α-羟基胆固醇、7β-羟基胆固醇、5,6-环氧胆固醇、3β-羟基胆甾-5-烯-7-酮和胆甾-3,5-二烯-7-酮。孕酮、胆甾-3,5-二烯、胆甾-2,4-二烯、胆甾-3,5,6-三醇和4-胆甾烯-3-酮被发现为次要成分，并通过它们的质谱、核磁共振氢谱和傅里叶变换红外光谱数据进行鉴定，并与标准品进行比较。胆甾-3,6-二酮、胆甾-4,6-二烯-3-酮、胆甾-2,4-二烯和胆甾-5,20(22)-二烯-3-醇仅以痕量被发现，并通过气相色谱/串联质谱光谱数据进行鉴定。由于胆固醇是EGS的主要成分，鉴定出的氧甾醇（OS）可能是胆固醇氧化产物。许多鉴定出的OS是已知的重要生物分子，在产生者和接受者生物体中发挥着至关重要的生理作用。我们在此报告这些甾醇对三种人类癌细胞系的影响，即K-562（慢性粒细胞白血病细胞系）、MDA MB-231（雌激素阳性乳腺癌细胞系）和MCF-7（雌激素阴性乳腺癌细胞系）。有趣的是，在所测试的OS对所用细胞类型之间观察到了显著（<0.05）的剂量差异。EGS中这些甾醇的存在可能有助于解释从EGS制备的B部分（FB）的一些生理活性方面，例如我们先前研究中报道的增强伤口和糖尿病溃疡愈合、抗炎作用和细胞毒性活性。本研究中在选定癌细胞系上确定的一些这些氧甾醇的抗增殖作用，特别是胆固醇3,5,6-三醇（#5），支持了我们先前的研究，并使它们成为人类应用研究的候选物。
