Kapoor Himanshi, Yadav Nalini, Chopra Madhu, Mahapatra Sushil Chandra, Agrawal Veena
Medicinal Plant Biotechnology and Applied Research Laboratory, Department of Botany, University of Delhi, Delhi, India.
Curr Cancer Drug Targets. 2017;17(1):74-88. doi: 10.2174/1570163813666161019143740.
Glioblastoma has been reckoned as the prime cause of death due to brain tumours, being the most invasive and lethal. Available treatment options, i.e. surgery, radiotherapy, chemotherapy and targeted therapies are not effective in improving prognosis, so an alternate therapy is insistent. Plant based drugs are efficient due to their synergistic action, multi-targeted approach and least side effects.
The anti-tumorous potential of Nardostachys jatamansi rhizome extract (NJRE) on U87 MG cell line was evaluated through various in vitro and in silico bio-analytical tools.
NJRE had a strong anti-proliferative effect on U87 MG cells, Its IC50 was 33.73±3.5, 30.59±3.4 and 28.39±2.9 μg/mL, respectively after 24, 48 and 72 h. NJRE at 30 μg/mL induced DNA fragmentation, indicating apoptosis, early apoptosis began in the cells at 20 μg/mL, whereas higher doses exhibited late apoptosis as revealed by dual fluorescence staining. NJRE at 60 and 80 μg /mL caused a G0/G1 arrest and at 20 and 40 μg/mL showed excessive nucleation and mitotic catastrophe in the cells. Immuno-blotting validated the apoptotic mode of cell death through intrinsic pathway. NJRE was harmless to normal cells. In silico docking of NJRE marker compounds: oroselol, jatamansinol, nardostachysin, jatamansinone and nardosinone have revealed their synergistic and multi-targeted interactions with Vestigial endothelial growth factor receptor 2 (VEGFR2), Cyclin dependent kinase 2 (CDK2), B-cell lymphoma 2 (BCL2) and Epidermal growth factor receptor (EGFR).
A strong dose specific and time dependent anti-tumorous potential of NJRE on U87 MG cells was seen. The extract can be used for the development of safe and multi-targeted therapy to manage glioblastoma, which has not been reported earlier.
胶质母细胞瘤被认为是脑肿瘤致死的主要原因，是最具侵袭性和致命性的。现有的治疗选择，即手术、放疗、化疗和靶向治疗，在改善预后方面并不有效，因此急需替代疗法。植物性药物因其协同作用、多靶点方法和最小的副作用而有效。
通过各种体外和计算机模拟生物分析工具评估甘松根茎提取物（NJRE）对U87 MG细胞系的抗肿瘤潜力。
NJRE对U87 MG细胞具有很强的抗增殖作用，在24、48和72小时后，其IC50分别为33.73±3.5、30.59±3.4和28.39±2.9 μg/mL。30 μg/mL的NJRE诱导DNA片段化，表明细胞凋亡，20 μg/mL时细胞开始出现早期凋亡，而更高剂量则表现为晚期凋亡，这通过双荧光染色得以揭示。60和80 μg/mL的NJRE导致G0/G1期阻滞，20和40 μg/mL时细胞出现过度核化和有丝分裂灾难。免疫印迹通过内源性途径验证了细胞死亡的凋亡模式。NJRE对正常细胞无害。NJRE标记化合物：欧缬草醇、甘松醇、甘松新酮、甘松酮和甘松螺酮的计算机模拟对接显示它们与血管内皮生长因子受体2（VEGFR2）、细胞周期蛋白依赖性激酶2（CDK2）、B细胞淋巴瘤2（BCL2）和表皮生长因子受体（EGFR）具有协同和多靶点相互作用。
观察到NJRE对U87 MG细胞具有很强的剂量特异性和时间依赖性抗肿瘤潜力。该提取物可用于开发安全的多靶点疗法来治疗胶质母细胞瘤，这在之前尚未见报道。
