蜂王浆诱导急性淋巴细胞白血病 (ALL) 衍生的 Nalm-6 细胞中 ROS 介导的细胞凋亡:揭示 ALL 的新治疗方法。
Royal jelly induces ROS-mediated apoptosis in acute lymphoblastic leukemia (ALL)-derived Nalm-6 cells: Shedding light on novel therapeutic approaches for ALL.
发表日期:2024
作者:
Somayeh Yazdanparast, Davood Bashash, Amirsalar Nikkhah Bahrami, Mohammad Ghorbani, Mehrdad Izadirad, Mehdi Bakhtiyaridovvombaygi, Seyede Zahra Hasanpour, Ahmad Gharehbaghian
来源:
Cell Death & Disease
摘要:
直到最近,急性淋巴细胞白血病(ALL)的常规化疗方案还被认为是一种有效的儿童治疗方法。然而,成人长期存活率不佳、疾病复发和药物引起的毒性需要新的治疗药物来治疗 ALL。如今,具有药理功效的天然产品在治疗不同癌症方面发挥着重要作用。在最有价值的天然产品中,蜜蜂蜂王浆 (RJ) 是最受赞赏的天然产品之一,它具有针对不同人类癌症的抗肿瘤活性。本研究旨在评估RJ对ALL来源的Nalm-6细胞的抗白血病特性和细胞毒性的分子机制。通过MTT法测定代谢活性。使用流式细胞术分析研究细胞凋亡、细胞周期中的细胞分布和细胞内活性氧(ROS)水平。此外,还进行了实时定量PCR(qRT-PCR)来检查各种调控基因的表达。RJ显着降低Nalm-6细胞的活力,但对正常细胞没有细胞毒性作用。此外,RJ 通过上调促凋亡基因同时降低抗凋亡基因表达来诱导 ROS 介导的细胞凋亡。结果概述了 FOXO4 和 Sirt1 的 ROS 依赖性上调通过 p21 上调抑制细胞向细胞周期 S 期的转变。自噬相关基因表达的 qRT-PCR 分析也表明,RJ 诱导 Naml-6 细胞中 BECN1 介导的自噬。总之,本研究表明 RJ 可作为一种有效的天然物质来诱导 ALL 细胞的程序性细胞死亡。然而,需要进一步研究来检验该化合物的药物应用。
Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees' royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells.The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes.RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells' transition to the S phase of the cell cycle through p21 up-regulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells.Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells' programmed cell death. However, further studies are required to examine this compound's pharmaceutical application.