Lange Ingo, Moschny Julia, Tamanyan Kamilla, Khutsishvili Manana, Atha Daniel, Borris Robert P, Koomoa Dana-Lynn
Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA.
Institute of Botany, National Academy of Sciences, Yerevan, Armenia.
Int J Oncol. 2016 Apr;48(4):1608-16. doi: 10.3892/ijo.2016.3373. Epub 2016 Feb 3.
Effective neuroblastoma (NB) treatments are still limited despite treatment options available today. Therefore, this study attempted to identify novel plant extracts that have anticancer effects. Cytotoxicity and increased intracellular calcium levels were determined using the Sulforhodamine B (SRB) assay and Fluo4-AM (acetoxymethyl) staining and fluorescence microscopy in NB cells in order to screen a library of plant extracts. The current study examined the anticancer effects of a dichloromethane extract from Scrophularia orientalis L. (Scrophulariaceae), a plant that has been used in Traditional Chinese Medicine. This extract contained highly potent agents that significantly reduced cell survival and increased calcium levels in NB cells. Further analysis revealed that cell death induced by this extract was associated with intracellular calcium release, opening of the MPTP, caspase 3- and PARP-cleavage suggesting that this extract induced aberrant calcium signaling that resulted in apoptosis via the mitochondrial pathway. Therefore, agents from Scrophularia orientalis may have the potential to lead to new chemo-therapeutic anticancer drugs. Furthermore, targeting intracellular calcium signaling may be a novel strategy to develop more effective treatments for NB.
尽管目前有多种治疗选择,但有效的神经母细胞瘤(NB)治疗方法仍然有限。因此,本研究试图鉴定具有抗癌作用的新型植物提取物。为了筛选植物提取物文库,在NB细胞中使用磺酰罗丹明B(SRB)测定法、Fluo4-AM(乙酰氧基甲基)染色和荧光显微镜检测细胞毒性和细胞内钙水平的升高。本研究考察了玄参科植物玄参(Scrophularia orientalis L.)二氯甲烷提取物的抗癌作用,该植物已被用于传统中药。该提取物含有高效活性成分,可显著降低NB细胞的存活率并提高细胞内钙水平。进一步分析表明,该提取物诱导的细胞死亡与细胞内钙释放、线粒体通透性转换孔(MPTP)开放、半胱天冬酶3和聚(ADP-核糖)聚合酶(PARP)裂解有关,提示该提取物诱导异常钙信号,通过线粒体途径导致细胞凋亡。因此,玄参中的活性成分可能有潜力开发出新的化疗抗癌药物。此外,靶向细胞内钙信号可能是开发更有效NB治疗方法的新策略。