Arya Malti, Mishra Nidhi, Singh Pooja, Tripathi Chandra B, Parashar Poonam, Singh Mahendra, Gupta Krishna P, Saraf Shubhini A
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Lucknow, India.
J Cell Physiol. 2019 Sep;234(9):15527-15536. doi: 10.1002/jcp.28200. Epub 2019 Jan 29.
Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer.
肌醇六磷酸(IP6)是几乎所有谷物和豆类中都含有的一种天然成分。已知它会引发多种抗血管生成表现。尽管其潜力巨大,但由于会螯合且从体内快速排泄,它未得到充分利用。扁豆凝集素是从菠萝蜜种子中提取的另一种天然成分,可靶向肿瘤细胞中过度表达的双糖。本研究旨在开发并评估一种包含IP6和扁豆凝集素的表面改性金纳米颗粒系统,该系统可能会使IP6对HCT - 15细胞系的凋亡作用最大化。通过还原后孵育法制备了负载IP6的扁豆凝集素 - 果胶 - 金纳米颗粒(IJP - GNPs)。对所开发的制剂进行了各种体外和计算机模拟研究,以探究其潜力。当HCT - 15细胞暴露于IJP - GNP时,使用3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐、微核和活性氧测定法测量,结果显示在剂量和时间依赖性方式上均产生了显著的凋亡效应。IJP - GNP在G0/G1期显示出细胞周期停滞。为了进一步探索化学预防机制,进行了计算机模拟研究。对接结果表明,IP6、P - GNP和扁豆凝集素的相互作用行为可靶向并抑制肿瘤形成活性,体外研究也支持这一点。综上所述,所有研究结果表明,负载IP6的纳米颗粒可能会增加未来结肠癌靶向给药策略的希望。