Promising anti-leukemic effect of Zataria multiflora extract in combination with doxorubicin to combat acute lymphoblastic leukemia cells (Nalm-6) (in vitro and in silico)

Abstract

One of the heterogeneous hematologic malignancies of the lymphocyte precursors is ALL. ALL has two incidence peaks that were determined in 2–5 years children and 60 years old adults. Cardiotoxicity of chemotherapeutic drugs is one of important side effects which may occur during or after chemotherapy period. The aim of this study was to evaluate the effect of ZME, Dox, and combinations on Nalm-6 cells. In this vein, the cell viability was assessed by Trypan blue and MTT assay. Evaluation of apoptosis was also analyzed by Annexin-V/PI staining. Moreover, the expression of Bax, Bcl-2, Bcl-xl, hTERT, c-Myc, P53, and P21 genes was detected by Real-Time PCR. Molecular docking as an in-silico method was performed for Bcl-2 and Bcl-xl proteins as well. Our achievements indicated that ZME had dose-dependent effect on Nalm-6 cells and ZME synergistically potentiated Dox effect. The expression of Bax, P53 and P21 genes increased although the expression of Bcl-2 genes decreased when cells treated with ZME/ Dox combination. Molecular docking showed the interactions of carvacrol and thymol in the active cavities of BCL2 and BCL-xl. Regarding to present study, ZME could be utilized as a combinatorial and potential drug for leukemic patients, which is under the treatment by Dox due to reducing the chemotherapy drug doses.