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姜黄素与细胞膜模型的相互作用通过 Langmuir 单分子层。

Interactions between curcumin and cell membrane models by Langmuir monolayers.

机构信息

Biocolloids and Fluid Physics Group, Department of Applied Physics, University of Granada, Campus Fuente Nueva, s/n, C.P. 18071, Granada, Spain; Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Cuesta del Hospicio, s/n, C.P. 18010, Granada, Spain.

Biocolloids and Fluid Physics Group, Department of Applied Physics, University of Granada, Campus Fuente Nueva, s/n, C.P. 18071, Granada, Spain; Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Cuesta del Hospicio, s/n, C.P. 18010, Granada, Spain.

出版信息

Colloids Surf B Biointerfaces. 2022 Sep;217:112636. doi: 10.1016/j.colsurfb.2022.112636. Epub 2022 Jun 17.

Abstract

Studying interactions between potential anticancer drugs and cell membrane models is of great interest to explore the capability of novel drugs in the development of anticancer treatments. Lipid membrane models are useful to understand cellular interactions and to discern drug mechanism action. Here, the interactions of curcumin, as a bioactive natural compound with anti-cancer properties, with both healthy and cancerous or tumor cell membrane models, based on Langmuir monolayers, have been studied. The healthy-cell membrane model is composed of cholesterol 67%, and saturated lipid dipalmitoylphosphatidylcholine 33%. The cancerous-cell-membrane-model is composed of a lower proportion of cholesterol, 25%, and unsaturated lipid sphingomyelin 75%. To compare their interaction with curcumin we report the compression isotherms registered for both lipid membrane models and curcumin in different proportions, their compression moduli and the thermodynamic interaction parameters. From this analysis, we evidence a destabilizing interaction between curcumin and the cancerous cell membrane model in comparison with the healthy one. This interaction is further visualized by micro-Brewster Angle and Atomic Force Microscopies. Our experiments show that the drug enhances cohesion in the healthy membrane model whereas it fluidifies the cancerous cell membrane model causing thermodynamic destabilization. These are useful results to improve the selectivity of the drug avoiding adverse side effects of most current anticancer therapies.

摘要

研究潜在抗癌药物与细胞膜模型之间的相互作用对于探索新型药物在癌症治疗开发中的能力具有重要意义。脂质膜模型有助于理解细胞相互作用,并辨别药物作用机制。在这里,基于 Langmuir 单分子层,研究了姜黄素(一种具有抗癌特性的生物活性天然化合物)与健康和癌变或肿瘤细胞膜模型的相互作用。健康细胞膜模型由胆固醇 67%和饱和脂质二棕榈酰磷脂酰胆碱 33%组成。癌变细胞膜模型由较低比例的胆固醇 25%和不饱和脂质神经鞘磷脂 75%组成。为了比较它们与姜黄素的相互作用,我们报告了两种脂质膜模型和不同比例的姜黄素的压缩等温线、压缩模量和热力学相互作用参数。从这项分析中,我们证明了姜黄素与癌变细胞膜模型的相互作用比健康细胞膜模型更具不稳定性。通过微布鲁斯特角和原子力显微镜进一步可视化了这种相互作用。我们的实验表明,该药物增强了健康膜模型的内聚力,而使癌变细胞膜模型变得更加流态,导致热力学不稳定性。这些结果有助于提高药物的选择性,避免大多数当前癌症治疗的不良反应。

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