Apoptosis Induction of Ganoderic Acid-A by Downregulating miR- 125b and miR-365a-3p in Nalm-6 cells

Acute lymphoblastic leukemia is the most common leukemia in children, which is associated with a high relapse rate despite prevalent therapies. Ganoderic acid-A (GAA) is one of the bioactive compounds of Ganoderma lucidum, which possesses potential antileukemic properties. This study aimed to investigate the effect of the GAA extract on the expression of microRNA and the apoptosis induction in the BCP-ALL cell line. In this case-control study, NALM-6 Cells were treated with the GAA extract and L-asparaginase separately. The cell viability and apoptosis rates were examined using MTT and flow cytometry, respectively. Moreover, the effect of the GAA on the expression of miR-125b and miR-365a-3p, in comparison to L-asparaginase, was studied using RT-PCR. The GAA extract inhibited the cell growth in a dose- and time-dependent manner. Moreover, the GAA extract significantly induced apoptosis compared to L-asparaginase (P=0.0021 vs. P=0.0112). The results showed that the treatment of Nalm-6 cells with GAA significantly reduced the expression of miR-125b (P< 0.0001) and miR-365a-3p (P= 0.0001). Furthermore, it was demonstrated that the downregulation of miR-125b and miR-365a-3p was surprisingly higher in the GA-treated Nalm-6 cells than in L-asparaginase-treated Nalm-6 cells. According to the findings, the GAA extract has antileukemic effects and can be used as a promising agent with fewer side effects in all treatments.