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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

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Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

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.

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Funding

This study gained the support of Kerman University of Medical Sciences by the Grant No. 98000523.

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Authors and Affiliations

  1. Department of Traditional Medicine, Faculty of Traditional Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Moghadari Masoud

  2. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Samareh Salavati pour Maryam

  3. Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran

    Samareh Salavati pour Maryam, Sattarzadeh Bardsiri Mahla, Kouhbananinejad Seyedeh Mehrnaz, Lashkari Mahla & Farsinejad Alireza

  4. Department of Hematology and Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran

    Sattarzadeh Bardsiri Mahla, Kouhbananinejad Seyedeh Mehrnaz, Lashkari Mahla & Farsinejad Alireza

  5. Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran

    Vahidi Reza

  6. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Kashani Bahareh

  7. Institute for Futures Studies, Modeling in Health Research Center, Kerman University of Medical Sciences, Kerman, Iran

    Dehesh Tania

Authors
  1. Moghadari Masoud
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  2. Samareh Salavati pour Maryam
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Contributions

AF and MM supervised all aspects of the work and proposed the original concept and designed the experiment. MS and RV participated in the data acquisition. MS and ML performed the real-time PCR experiments and interpretation of obtained results. Interpretation of immunoprofiling was performed by MK contributed to the data analysis. RV and BK contributed to writing the manuscript.

Corresponding authors

Correspondence to Vahidi Reza or Farsinejad Alireza.

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Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethics Approval

The study gained the approval of the ethical committee of Kerman University of Medical Sciences with the Ethics approval code of IR.KMU.REC.1398.397.

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Masoud, M., Maryam, S.S.p., Mahla, S.B. et al. Elevated Bax/Bcl-2 Ratio: A Cytotoxic Mode of Action of Kermanian Propolis Against an Acute Lymphoblastic Leukemia Cell Line, NALM-6. Indian J Hematol Blood Transfus 38, 649–657 (2022). https://doi.org/10.1007/s12288-022-01522-4

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