The effect of simultaneous administration of arsenic trioxide and microvesicles derived from human bone marrow mesenchymal stem cells on cell proliferation and apoptosis of acute myeloid leukemia cell line

Abstract

Acute Promyelocytic Leukemia is one of the most prevalent forms of leukemia which has been treated with arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Although, ATRA and ATO are broadly accessible and administrated, some adverse side effects have been reported recently. Nowadays, microvesicles (MVs) are considered as a potential therapeutic agent. Their capacity to alter the behavior of the cells is one of the most controversial issues. In this study, we investigated apoptotic effects of MVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs) in combination with ATO on NB4 cell line. MVs were isolated by ultra-centrifugation. After 7 days, MTT assay, Annexin-V-fluorescein staining assay and RT-qPCR for BCL-2, KI67, BAX genes expression were performed. The results showed lower cell viability rate, higher apoptosis ratio, higher BAX gene, and lower KI67 and BCL-2 genes' expression in cells exposed to MVs in combination with ATO compared to cells treated with each agent alone and non-treated control. We showed that MVs in combination with ATO had more apoptotic effect on NB4 cell line than each agent alone. MVs in combination with ATO in APL treatment might play an effective therapeutic role with fewer adverse side effects compared to any other agents.