Inhibition of human neuroblastoma cells through ROS-activation by naringin

A. Arthi, Vijaya Lobo, R. Vidhyavathi, E. Raj, Arun Kumar Ramu
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Abstract

Current remedial options for recurrent neuroblastoma have poor outcomes that warrant the development of novel restorative methodologies. Naringin (4',5,7-trihydroxy-flavanone-7-rhamnoglucoside), a naturally occurring flavonoid present in various Indian medicinal spices, has been shown anti-inflammatory and anticancer activities. In this paper, naringin was used to evaluate its anti-proliferative impact on human SK-N-MC neuroblastoma cell lines. Cytotoxicity and reactive oxygen species (ROS) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) test, respectively. It was found that naringin induced 100% cancer cell inhibition at 120 μM, hence, 30, 45 and 60 μM doses were chosen for anticancer examinations. Significant apoptosis was recorded at 60 μM dose of naringin which was found associated with the generation of ROS. Overall, the investigation indicated that naringin induces apoptosis in SK-N-MC cells to produce ROS in a mitochondria-dependent and independent manner. In conclusion, at high doses, naringin adequately inhibits the growth of solid neuroblastoma tumour and has high bioavailability, particular toxicity and a high margin of security, making it a possible candidate for a potential clinical treatment of neuroblastoma.
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柚皮苷通过ros活化抑制人神经母细胞瘤细胞
目前治疗复发性神经母细胞瘤的方法效果不佳,需要开发新的修复方法。柚皮苷(4′,5,7-三羟基黄酮-7-鼠李糖糖苷)是一种天然存在的类黄酮,存在于各种印度药用香料中,具有抗炎和抗癌活性。本文用柚皮苷对人SK-N-MC神经母细胞瘤细胞株进行了抗增殖作用的研究。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)法和2,7-二氯双氢荧光素(DCFH-DA)法测定细胞毒性和活性氧(ROS)。结果表明,柚皮苷在120 μM的剂量下对癌细胞的抑制率为100%,因此选择30、45和60 μM的剂量进行抗癌试验。柚皮苷在60 μM剂量下出现明显的细胞凋亡,并与ROS的产生有关。综上所述,研究表明柚皮苷诱导SK-N-MC细胞凋亡,以线粒体依赖和独立的方式产生ROS。综上所述,在高剂量下,柚皮苷能充分抑制实体神经母细胞瘤肿瘤的生长,具有较高的生物利用度、特殊的毒性和较高的安全边际,使其成为神经母细胞瘤临床治疗的潜在候选药物。
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