Biswas Indrani, Precilla Daisy S, Kuduvalli Shreyas S, Ramachandran Muralidharan Arumugam, Akshaya S, Raman Venkat, Prabhu Dhamodharan, Anitha T S
Mahatma Gandhi Medical Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to-be University), Puducherry, 607402 India.
Department of Visual Neurosciences, Singapore Eye Research Institute, Singapore, 169856 Singapore.
3 Biotech. 2023 Dec;13(12):397. doi: 10.1007/s13205-023-03814-6. Epub 2023 Nov 14.
Glioma coined as a "butterfly" tumor associated with a dismal prognosis. Marine algal compounds with the richest sources of bioactive components act as significant anti-tumor therapeutics. However, there is a paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. Therefore, the present study aimed to evaluate the synergistic anti-proliferative, anti-inflammatory and pro-apoptotic effects of Fucoidan with Temozolomide in in vitro and in silico experimental setup The anti-proliferative effects of Temozolomide and Fucoidan were evaluated on C6 glioma cells by MTT and migration assay. Modulation of inflammatory markers and apoptosis induction was affirmed at the morphological and transcriptional level by dual staining and gene expression. Molecular docking (MD) and molecular dynamics simulation (MDS) studies were performed against the targets to rationalize the inhibitory effect. The dual-drug combination significantly reduced the cell viability and migration of glioma cells in a synergistic dose-dependent manner. At the molecular level, the dual-drug combination significantly down-regulated inflammatory genes with a concomitant upregulation of pro-apoptotic marker. In consensus with our in vitro findings, molecular docking and simulation studies revealed that the anti-tumor ligands: Temozolomide, Fucoidan with 5-(3-Methy1-trizeno)-imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) had the potency to bind to the inflammatory proteins at their active sites, mediated by H-bonds and other non-covalent interactions. The dual-drug combinatorial treatment synergistically inhibited the proliferation, migration of glioma cells and promoted apoptosis; conversely with the down-regulation of inflammatory genes. However, pre-clinical experimental evidence is warranted for the possible translation of this combination.
The online version contains supplementary material available at 10.1007/s13205-023-03814-6.
胶质瘤被称为“蝴蝶”肿瘤，预后不佳。富含生物活性成分的海洋藻类化合物可作为重要的抗肿瘤治疗药物。然而，关于岩藻多糖增强替莫唑胺抗胶质瘤疗效的研究较少。因此，本研究旨在通过体外和计算机模拟实验装置评估岩藻多糖与替莫唑胺的协同抗增殖、抗炎和促凋亡作用。通过MTT和迁移试验评估替莫唑胺和岩藻多糖对C6胶质瘤细胞的抗增殖作用。通过双重染色和基因表达在形态学和转录水平上确认炎症标志物的调节和凋亡诱导。进行分子对接（MD）和分子动力学模拟（MDS）研究以阐明抑制作用的合理性。双药联合以协同剂量依赖性方式显著降低胶质瘤细胞的活力和迁移。在分子水平上，双药联合显著下调炎症基因，同时上调促凋亡标志物。与我们的体外研究结果一致，分子对接和模拟研究表明，抗肿瘤配体：替莫唑胺、岩藻多糖与5-（3-甲基-三氮烯）-咪唑-4-甲酰胺（MTIC）和4-氨基-5-咪唑甲酰胺（AIC）能够通过氢键和其他非共价相互作用在其活性位点与炎症蛋白结合。双药联合治疗协同抑制胶质瘤细胞的增殖、迁移并促进凋亡；反之则下调炎症基因。然而，这种联合治疗的潜在转化需要临床前实验证据支持。
在线版本包含可在10.1007/s13205-023-03814-6获取的补充材料。
