Promising Anti-leukemic Effect of Zataria Multiflora Extract in Combination with Doxorubicin to Combat Acute Lymphoblastic Leukemia Cells (Nalm-6)

Purpose: One of the heterogeneous hematologic malignancies of the lymphocyte precursors or lymphoblasts 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 effect which may occur during or after chemotherapy period. Methods: The aim of this study was to evaluate the effect of Zataria Multiflora extract (ZME), DOX, and ZME/DOX combination 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/7-PI staining. Moreover, the expression of Bax, Bcl-2, hTERT, c-Myc, P53, and P21 genes was detected by Real-Time PCR. Molecular docking as an in-silico method was performed for BCL2 and P53 as well. Result: 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, hTERT, and c-Myc 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 P53. Conclusions: 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.