Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wrocław, Poland.
Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.
Bioelectrochemistry. 2022 Oct;147:108199. doi: 10.1016/j.bioelechem.2022.108199. Epub 2022 Jun 30.
Catechin is a bioflavonoid known for its anti-cancer properties. In the present study, we combined theoretical and experimental approaches to reveal the potential of catechin application in the electroporation (EP) or electrochemotherapy (ECT) of pancreatic cancer cells. The molecular dynamics simulations were implemented to examine the interactions of catechin with a model of a membrane, its influence on the membrane's thickness, and the impact of the catechin-membrane interaction on the pore formation. The data were confronted with experimental measurement of the threshold electric field required for permeabilization of pancreatic cancer cells to a fluorescent dye YO-PRO-1. Further, we examined the influence of catechin on cell viability following electroporation with cisplatin or calcium ions. Finally, we investigated the catechin impact on four proteins associated with multidrug resistance: P-glycoprotein, MRP1, BCRP, and LRP. We demonstrated that catechin may boost the effects of electroporation through various mechanisms: i) increasing the cell permeability prior to electroporation ii) increasing the electroporation threshold iii) sensitization of cells to chemotherapeutic compounds. We showed that catechin incubation influences mRNA levels and mitigates the immunoreactivity of Pgp, MRP1, BCRP, and LRP but these changes did not translate to the efficacy of electrochemotherapy.
表儿茶素是一种生物类黄酮，具有抗癌特性。在本研究中，我们结合理论和实验方法，揭示了表儿茶素在胰腺癌细胞电穿孔（EP）或电化学治疗（ECT）中的应用潜力。通过分子动力学模拟，研究了表儿茶素与膜模型的相互作用、对膜厚度的影响，以及表儿茶素-膜相互作用对孔形成的影响。将这些数据与用荧光染料 YO-PRO-1 渗透胰腺癌细胞所需的临界电场的实验测量结果进行了对比。此外，我们还研究了表儿茶素对顺铂或钙离子电穿孔后细胞活力的影响。最后，我们研究了表儿茶素对与多药耐药相关的四种蛋白的影响：P-糖蛋白、MRP1、BCRP 和 LRP。我们证明，表儿茶素可以通过多种机制增强电穿孔的效果：i）在电穿孔前增加细胞通透性；ii）增加电穿孔阈值；iii）使细胞对化疗药物敏感。我们发现表儿茶素孵育会影响 mRNA 水平，并减轻 Pgp、MRP1、BCRP 和 LRP 的免疫反应性，但这些变化并未转化为电化学治疗的疗效。
