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Elevated Bax/Bcl-2 Ratio: A Cytotoxic Mode of Action of Kermanian Propolis Against an Acute Lymphoblastic Leukemia Cell Line, Nalm-6 Publisher



Masoud M1 ; Maryam SS2, 3 ; Mahla SB3, 4 ; Mehrnaz KS3, 4 ; Mahla L3, 4 ; Reza V5 ; Bahareh K6 ; Tania D7 ; Alireza F3, 4
Authors
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Authors Affiliations
  1. 1. Department of Traditional Medicine, Faculty of Traditional Medicine, Kerman University of Medical Sciences, Kerman, Iran
  2. 2. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran
  4. 4. Department of Hematology and Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran
  5. 5. Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
  6. 6. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Institute for Futures Studies, Modeling in Health Research Center, Kerman University of Medical Sciences, Kerman, Iran

Source: Indian Journal of Hematology and Blood Transfusion Published:2022


Abstract

Currently, alternative cancer remedies, especially herbal-derived medicines, have attracted great interest. Propolis, a honeybee-produced naturopathic formulation, is an available, affordable, and safe example of such remedies with different content according to its geographic location. Findings regarding the protective properties of this resinous substance across numerous pathological conditions are promising. Although the anti-tumor effects of propolis from different origins have been explored to some degree, yet there is no study on the effects of Kermanian propolis in the treatment of hematologic malignancies. Accordingly, the objective of the present experiment was to divulge the anti-tumor potential of this bioactive substance both as monotherapy and in combination with doxorubicin against an acute lymphoblastic leukemia cell line (NALM-6).The viability of cells treated with Kermanian propolis (5–500 μg/mL) and doxorubicin (5–100 μg/mL) was analyzed during 72 h. Based on the MTT results, the best incubation time, IC50 concentrations, and finally the cytotoxicity of the combination therapy were ascertained. Next, the apoptotic rate and expression of apoptosis-related genes (Bcl-2 and Bax) were assessed in mono and combination therapies using flow cytometry and real-time PCR assays, respectively. Kermanian propolis and doxorubicin have impressive tumor-suppressing activity in a dose-dependent manner (IC50 concentrations: 100 and 40 μg/mL respectively). The best incubation time was considered 48 h. For the combination approach, 50 and 10 μg/mL were determined as optimum concentrations of the compounds. The selected concentrations induced notable apoptosis in the studied cells through significant (P < 0.01) upregulation of Bax/Bcl-2 level. The present study clearly suggests that Kermanian propolis, as an adjunct treatment option, has a promising apoptosis-induced cell death potential in the NALM-6 cell line. © 2022, Indian Society of Hematology and Blood Transfusion.
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