文章：

《双色十蕊木中δ-杜松烯对人类细胞黏附与侵袭蛋白选择性抑制作用的计算机模拟与体外实验评估》

In Silico and In Vitro Evaluation of δ-cadinene fromDecatropis bicoloras a Selective Inhibitor of Human Cell Adhesion and Invasion Proteins

原文发布日期：29 August 2025

DOI: 10.3390/cancers17172839

类型: Article

开放获取: 是

英文摘要：

Background: Breast cancer is a complex, multifactorial malignancy characterized by the uncontrolled proliferation of epithelial cells, with certain subtypes exhibiting resistance to conventional therapies. Plant-derived essential oils have been proposed as potential anticancer agents due to their bioactive compounds. Recent studies have demonstrated thatDecatropis bicoloressential oil exhibits activity against breast cancer, attributed to diverse secondary metabolites such as δ-cadinene. Aberrant expression of adhesion and invasion proteins, including MMPs, CD44, N-cadherin, and ZEB-2, are key signs of breast cancer progression and metastasis; they represent relevant molecular targets.Objectives: To investigate the interaction of δ-cadinene with these proteins using in silico approaches and in vitro evaluations.Methods: In silico analyses were conducted to assess the interaction and stability of δ-cadinene with target proteins. In vitro assays, including cytotoxicity, morphological analysis, and cell invasion assays, were performed using MDA-MB-231 and MCF10-A cell lines.Results: Interaction analysis suggest that δ-cadinene interacts with key catalytic residues in MMP-2, sharing features with Quercetin. Blind docking revealed a second high-affinity site in the Fibronectin type II domain. Molecular dynamics simulations confirmed the stability of these complexes. In vitro studies showed that δ-cadinene significantly reduced MDA-MB-231 cell viability in a concentration-dependent manner, without affecting MCF10-A cells, and significantly inhibited invasion and MMP-2 activity after 24 h.Conclusions: δ-cadinene exhibits selective cytotoxic and anti-invasive activity in MDA-MB-231 cells, likely through dual inhibition of the catalytic and adhesion domains of MMP-2. These findings support δ-cadinene as a potential candidate for future therapeutic development in metastatic breast cancer.

摘要翻译： 

背景：乳腺癌是一种复杂的多因素恶性肿瘤，其特征是上皮细胞不受控制地增殖，某些亚型对常规疗法表现出耐药性。植物来源的精油因其生物活性化合物而被认为是潜在的抗癌剂。最近的研究表明，双色十萼木精油对乳腺癌具有活性，这归因于其多种次生代谢产物，如δ-杜松烯。包括基质金属蛋白酶、CD44、N-钙黏蛋白和ZEB-2在内的黏附和侵袭蛋白的异常表达是乳腺癌进展和转移的关键标志；它们是相关的分子靶点。 目的：通过计算机模拟方法和体外评估研究δ-杜松烯与这些蛋白的相互作用。 方法：进行计算机模拟分析以评估δ-杜松烯与靶蛋白的相互作用和稳定性。使用MDA-MB-231和MCF10-A细胞系进行体外实验，包括细胞毒性、形态学分析和细胞侵袭实验。 结果：相互作用分析表明，δ-杜松烯与MMP-2的关键催化残基相互作用，与槲皮素具有相似特征。盲对接揭示了纤维连接蛋白II型结构域中的第二个高亲和力位点。分子动力学模拟证实了这些复合物的稳定性。体外研究表明，δ-杜松烯以浓度依赖性方式显著降低MDA-MB-231细胞的活力，而不影响MCF10-A细胞，并在24小时后显著抑制侵袭和MMP-2活性。 结论：δ-杜松烯在MDA-MB-231细胞中表现出选择性的细胞毒性和抗侵袭活性，可能通过双重抑制MMP-2的催化结构域和黏附结构域实现。这些发现支持δ-杜松烯作为未来转移性乳腺癌治疗开发的潜在候选药物。

原文链接：

In Silico and In Vitro Evaluation of δ-cadinene fromDecatropis bicoloras a Selective Inhibitor of Human Cell Adhesion and Invasion Proteins