Department of Plant Pathology, Assam Agricultural University, Jorhat, India.
Department of Biochemistry, North-Eastern Hill University, Shillong, India.
J Biomol Struct Dyn. 2024 Nov;42(18):9705-9719. doi: 10.1080/07391102.2023.2272743. Epub 2023 Oct 23.
The tumour suppressor protein PTEN is often down-regulated in non-small cell lung cancer. A major protein promoting the lowering of the PTEN protein is WWP2. Polyphenols have been shown to promote the expression of tumour suppressor genes like PTEN. We carry out the study to check for the ability of apigenin to bind with the WWP2 protein using investigation comprising docking and simulation. We checked for the cytotoxic effect of apigenin upon the non-small cell lung cancer cell line NCI-H23. We checked the PTEN expression status at the gene and protein levels. The expression levels of the apoptotic regulators BCL2, BAX and CASPASE3 genes along with the activity levels of the caspase-3 protein were checked. The ultrastructure of the cells was analysed. Our Autodock analysis showed that apigenin bound favourably with the WWP2 protein. Molecular dynamics simulation revealed that apigenin increased the parameters of RMSD, Rg and SASA when bound with the WWP2 protein. The protein-ligand complex had hydrogen bonding and majorly van der Wal's interactions. PCA analysis revealed greater fluctuations in the apigenin-bound state of the protein. The mutant form of the WWP2 revealed similar results in the presence of apigenin. Apigenin showed efficacy against the NCI-H23 cell line and promoted PTEN protein levels, lowered BCL2 gene expression and up-regulated BAX and CASPASE3 gene expression. Increased caspase-3 activity and ultra-structural analysis revealed the occurrence of apoptosis. Thus the binding of apigenin with WWP2 could promote PTEN protein levels and lead to apoptotic activity in NCI-H23 cells.Communicated by Ramaswamy H. Sarma.
抑癌蛋白 PTEN 在非小细胞肺癌中经常下调。促进 PTEN 蛋白降低的主要蛋白质是 WWP2。多酚已被证明能促进肿瘤抑制基因如 PTEN 的表达。我们进行了这项研究，以检查芹菜素与 WWP2 蛋白结合的能力，使用包括对接和模拟的研究。我们检查了芹菜素对非小细胞肺癌细胞系 NCI-H23 的细胞毒性作用。我们检查了基因和蛋白水平的 PTEN 表达状态。检查了凋亡调节剂 BCL2、BAX 和 CASPASE3 基因的表达水平以及 caspase-3 蛋白的活性水平。分析了细胞的超微结构。我们的 Autodock 分析表明，芹菜素与 WWP2 蛋白结合良好。分子动力学模拟表明，芹菜素与 WWP2 蛋白结合时增加了 RMSD、Rg 和 SASA 的参数。蛋白-配体复合物具有氢键和主要的范德华相互作用。PCA 分析显示，在蛋白结合状态下，蛋白的波动更大。在存在芹菜素的情况下，WWP2 的突变形式也显示出类似的结果。芹菜素对 NCI-H23 细胞系有效，能促进 PTEN 蛋白水平，降低 BCL2 基因表达，上调 BAX 和 CASPASE3 基因表达。增加 caspase-3 活性和超微结构分析显示发生了细胞凋亡。因此，芹菜素与 WWP2 的结合可以促进 NCI-H23 细胞中 PTEN 蛋白水平的升高，并导致细胞凋亡活性。由 Ramaswamy H. Sarma 交流。
