Somayeh Yazdanparast - Laboratory Hematology and Blood Bank Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Davood Bashash - Laboratory Hematology and Blood Bank Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Amirsalar Nikkhah Bahrami - Laboratory Hematology and Blood Bank Department, School of Allied Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
Mohammad Ghorbani - Laboratory Hematology and Transfusion Medicine, Department of Pathology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
Mehrdad Izadirad - Laboratory Hematology and Blood Bank Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mehdi Bakhtiyaridovvombaygi - Laboratory Hematology and Blood Bank Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Ahmad Gharehbaghian - Laboratory Hematology and Blood Bank Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Objective(s): 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-۶ cells.Materials and Methods: 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. Results: RJ significantly decreased the viability of Nalm-۶ 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 FOXO۴ and Sirt۱ inhibits the cells’ transition to the S phase of the cell cycle through p۲۱ up-regulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN۱ mediated autophagy in Naml-۶ cells.Conclusion: 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.

Acute lymphoblastic - leukemia (ALL), Apoptosis, Nalm-۶, Reactive oxygen species - (ROS), Royal jelly (RJ)