Gill Balraj Singh, Kumar Sanjeev
Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India.
Centre for Plant Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India.
Tumour Biol. 2016 Oct;37(10):14271-14290. doi: 10.1007/s13277-016-5291-8. Epub 2016 Sep 3.
Receptor tyrosine kinases (RTKs) are transmembrane high-affinity surface receptors responsible for cell migration, adhesion, apoptosis, metabolism, and cell proliferation activities in various cancers. Minute aberration in the RTK signaling modulates the downstream signaling pathways that results in cancer. Ganoderic acid is a triterpene isolated from Ganoderma lucidum, which is renowned for its therapeutics effect, especially in cancer. The present study discusses receptor-based molecular docking of insulin receptor (IR), insulin-like growth factor receptor 1 (IGFR-1), vascular endothelial growth factor receptor-1 (VEGFR-1), vascular endothelial growth factor receptor-2 (VEGFR-2), and estrogen receptor (ER) with 50 isoforms of ganoderic acid along with natural inhibitors. These receptors were assessed for toxicity (ADMET) by using Maestro 9.6 (Schrödinger Inc). The calculated docking free energy yielded an excellent dock score for the ganoderic acid when docked with proteins IR, IGFR-1, VEGFR-1, VEGFR-2, and ER, suggesting its potential in combating cancer. Protein-ligand profile highlighted the binding interactions comprising lipophilic, hydrogen bonding, pi-pi stacking interactions, and noncovalent bonding which play a pivotal role in targeting cancer. In silico studies revealed structure of ganoderic acid A as best isoforms among 50 isoforms which exhibits biological activity in liver cancer cells. Ganoderic acids A significantly decrease the viability, proliferation, and oxidative stress in a dose-dependent manner in liver cancer cells.
受体酪氨酸激酶（RTKs）是跨膜高亲和力表面受体，负责多种癌症中的细胞迁移、黏附、凋亡、代谢和细胞增殖活动。RTK信号传导中的微小异常会调节导致癌症的下游信号通路。灵芝酸是从灵芝中分离出的一种三萜类化合物，以其治疗效果而闻名，尤其是在癌症治疗方面。本研究讨论了胰岛素受体（IR）、胰岛素样生长因子受体1（IGFR-1）、血管内皮生长因子受体-1（VEGFR-1）、血管内皮生长因子受体-2（VEGFR-2）和雌激素受体（ER）与50种灵芝酸异构体以及天然抑制剂基于受体的分子对接。使用Maestro 9.6（薛定谔公司）评估这些受体的毒性（ADMET）。当灵芝酸与蛋白质IR、IGFR-1、VEGFR-1、VEGFR-2和ER对接时，计算得到的对接自由能产生了优异的对接分数，表明其在抗癌方面的潜力。蛋白质-配体图谱突出了包括亲脂性、氢键、π-π堆积相互作用和非共价键在内的结合相互作用，这些相互作用在靶向癌症中起着关键作用。计算机模拟研究表明，灵芝酸A是50种异构体中表现出最佳生物活性的异构体，在肝癌细胞中具有显著的生物活性。灵芝酸A以剂量依赖性方式显著降低肝癌细胞的活力、增殖和氧化应激。
