Othman Hemn, Rahman Heshu, Mohan Syam, Aziz Sadat, Marif Hardi, Ford Dianne, Abdulsamad Nozlena, Amin Kawa, Abdullah Rasedee
Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia.
College of Pharmacy, University of Sulaimani, Sulaymaniyah, Kurdistan Region, Iraq.
Evid Based Complement Alternat Med. 2020 Aug 19;2020:8764096. doi: 10.1155/2020/8764096. eCollection 2020.
This study investigated the antileukemic activity of palladium nanoparticles (Pd@W.tea-NPs) mediated by white tea extract in a murine model. The cell viability effect of Pd@W.tea-NPs, "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of Pd@W.tea-NPs in WEHI-3B cells were evaluated. The effects of Pd@W.tea-NPs administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. Pd@W.tea-NPs reduced the viability of WHEI-3B cells with IC 7.55 g/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. Pd@W.tea-NPs increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by Pd@W.tea-NPs with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. Pd@W.tea-NPs afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.
本研究在小鼠模型中探究了白茶提取物介导的钯纳米颗粒(Pd@W.tea-NPs)的抗白血病活性。分别测定了Pd@W.tea-NPs、“空白”钯纳米颗粒及单独的白茶提取物对小鼠白血病WEHI-3B细胞和正常小鼠成纤维细胞(3T3细胞)的细胞活力影响。评估了Pd@W.tea-NPs对WEHI-3B细胞的凋亡和细胞周期阻滞作用。评估了以50和100 mg/kg的剂量每天口服Pd@W.tea-NPs给药28天对白血病小鼠的影响。Pd@W.tea-NPs在72小时时以IC 7.55 μg/ml降低了WHEI-3B细胞的活力。单独的空白钯纳米颗粒和白茶提取物对WHEI-3B细胞活力及正常成纤维细胞的影响较小。Pd@W.tea-NPs增加了膜联蛋白V阳性的WHEI-3B细胞比例并诱导G2/M期细胞周期阻滞。Pd@W.tea-NPs使脾脏中的白血病细胞减少,同时Bax/Bcl-2以及细胞色素C蛋白和mRNA水平升高,表明线粒体凋亡途径被激活。这些作用与全反式维甲酸的作用相似,而空白钯纳米颗粒未观察到此类作用。Pd@W.tea-NPs对白血病具有治疗效果,可能是通过激活凋亡信号的线粒体途径实现的,因此似乎是有吸引力的新型抗癌药物开发潜在候选物。