Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, The Islamic University, Najaf, Iraq.
Sci Rep. 2022 Sep 8;12(1):15235. doi: 10.1038/s41598-022-18557-2.
Resveratrol (RSV), a non-flavonoid stilbene polyphenol, possesses anti-carcinogenic activities against all the major stages of cancer. Zein nanoparticles (ZN NPs) have been utilized successfully in delivery of variant therapeuticals by virtue of their histocompatible nature. The goal of this work was to comparatively explore the antiproliferative, pro-apoptotic and oxidative stress potentials of RSV-ZN NPs versus RSV against human colorectal carcinoma HCT-116 cells. ZN-RSV NPs were developed and assayed for particle size analysis and RSV diffusion. The selected formula obtained 137.6 ± 8.3 nm as mean particle size, 29.4 ± 1.8 mV zeta potential, 92.3 ± 3.6% encapsulation efficiency. IC of the selected formula was significantly lower against HCT-116 cells versus Caco-2 cells. Also, significantly enhanced cellular uptake was generated from RSV-ZN NPs versus free RSV. Enhanced apoptosis was concluded due to increased percentage cells in G2-M and pre-G1 phases. The pro-apoptotic potential was explained by caspase-3 and cleaved caspase-3 increased mRNA expression in addition to NF-κB and miRNA125b decreased expression. Biochemically, ZN-RSV NPs induced oxidative stress as demonstrated by enhanced reactive oxygen species (ROS) generation and endothelial nitric oxide synthase (eNOS) isoenzyme increased levels. Conclusively, ZN-RSV NPs obtained cell cycle inhibition supported with augmented cytotoxicity, uptake and oxidative stress markers levels in HCT-116 tumor cells in comparison with free RSV. These results indicated intensified chemopreventive profile of RSV due to effective delivery utilizing ZN nano-dispersion against colorectal carcinoma HCT-116 cells.
白藜芦醇(RSV)是一种非黄酮类芪多酚,具有针对癌症所有主要阶段的抗癌活性。玉米醇溶蛋白纳米粒(ZN NPs)由于其组织相容性而成功地用于各种治疗药物的递送。本工作的目的是比较 RSV-ZN NPs 与 RSV 对人结肠直肠癌细胞 HCT-116 的抗增殖、促凋亡和氧化应激潜力。开发了 ZN-RSV NPs 并进行了粒径分析和 RSV 扩散测定。获得的最佳配方的平均粒径为 137.6±8.3nm,Zeta 电位为 29.4±1.8mV,包封效率为 92.3±3.6%。与 Caco-2 细胞相比,最佳配方的 IC 对 HCT-116 细胞的抑制作用明显更强。此外,与游离 RSV 相比,RSV-ZN NPs 产生了明显增强的细胞摄取。由于 G2-M 和 Pre-G1 期的细胞百分比增加,推断出增强的细胞凋亡。caspase-3 和 cleaved caspase-3 的 mRNA 表达增加以及 NF-κB 和 miRNA125b 的表达降低解释了促凋亡潜力。从生化角度来看,ZN-RSV NPs 诱导了氧化应激,表现为活性氧(ROS)生成增加和内皮型一氧化氮合酶(eNOS)同工酶水平增加。总之,与游离 RSV 相比,ZN-RSV NPs 获得的细胞周期抑制作用支持 HCT-116 肿瘤细胞中细胞摄取和氧化应激标志物水平的增加以及细胞摄取和氧化应激标志物水平的增加。这些结果表明,由于利用 ZN 纳米分散体有效传递,RSV 的化学预防谱得到了加强,对 HCT-116 结肠直肠癌细胞具有更强的作用。