Mishra Rachana, Kaur Gurcharan
Department of Biotechnology, Guru Nanak Dev University, Amritsar, 143005, Punjab, India.
Mol Neurobiol. 2015 Aug;52(1):719-33. doi: 10.1007/s12035-014-8892-5. Epub 2014 Oct 4.
Children diagnosed with neuroblastomas often suffer from severe side as well as late effects of conventional treatments like chemotherapy and radiotherapy. Recent advances in understanding of molecular pathways involved in cellular differentiation and apoptosis have helped in the development of new therapeutic approach based on differentiation-based therapy of malignant tumours. Natural medicines with their holistic therapeutic approach are known to selectively eliminate cancer cells thus provide a better substitute for the conventional treatment modes. The current study was aimed to investigate the anti-cancer potential of aqueous ethanolic extract of Tinospora cordifolia (TCE) using IMR-32 human neuroblastoma cell line as a model system. TCE is highly recommended in Ayurveda for its general body and metal health-promoting properties. TCE treatment was seen to arrest the majority of cells in G0/G1 phase and modulated the expression of DNA clamp sliding protein (PCNA) and cyclin D1. Further, TCE-treated cells showed differentiation as revealed by their morphology and the expression of neuronal cell specific differentiation markers NF200, MAP-2 and NeuN in neuroblastoma cells. The differentiated phenotype was associated with induction of senescence and pro-apoptosis pathways by enhancing expression of senescence marker mortalin and Rel A subunit of nuclear factor kappa beta (NFkB) along with decreased expression of anti-apoptotic marker, Bcl-xl. TCE exhibited anti-metastatic activity and significantly reduced cell migration in the scratched area along with downregulation of neural cell adhesion molecule (NCAM) polysialylation and secretion of matrix metalloproteinases (MMPs). Our data suggest that crude extract or active phytochemicals from this plant may be a potential candidate for differentiation-based therapy of malignant neuroblastoma cells.
被诊断患有神经母细胞瘤的儿童经常遭受传统治疗（如化疗和放疗）的严重副作用以及后期影响。对细胞分化和凋亡所涉及分子途径理解的最新进展有助于基于恶性肿瘤分化疗法开发新的治疗方法。天然药物以其整体治疗方法而闻名，已知能选择性地消除癌细胞，从而为传统治疗模式提供更好的替代方案。本研究旨在以IMR - 32人神经母细胞瘤细胞系为模型系统，研究匙叶甘遂水乙醇提取物（TCE）的抗癌潜力。在阿育吠陀医学中，TCE因其对全身健康和促进金属健康的特性而被高度推荐。TCE处理可见使大多数细胞停滞在G0/G1期，并调节DNA夹滑动蛋白（PCNA）和细胞周期蛋白D1的表达。此外，TCE处理的细胞通过其形态以及神经母细胞瘤细胞中神经元细胞特异性分化标志物NF200、MAP - 2和NeuN的表达显示出分化。分化表型与衰老和促凋亡途径的诱导相关，通过增强衰老标志物mortalin和核因子κB（NFkB）的Rel A亚基的表达以及抗凋亡标志物Bcl - xl表达的降低。TCE表现出抗转移活性，并显著减少划痕区域的细胞迁移，同时下调神经细胞黏附分子（NCAM）多聚唾液酸化和基质金属蛋白酶（MMPs）的分泌。我们的数据表明，该植物的粗提物或活性植物化学物质可能是恶性神经母细胞瘤细胞分化疗法的潜在候选物。
