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Britannin, a sesquiterpene lactone induces ROS-dependent apoptosis in NALM-6, REH, and JURKAT cell lines and produces a synergistic effect with vincristine

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Abstract

Background

Britannin, a Sesquiterpene Lactone isolated from Inula aucheriana, has recently gained attraction in the therapeutic fields due to its anti-tumor properties. This study was designed to evaluate the effect of this agent on Acute Lymphoblastic Leukemia (ALL) cell lines, either as a monotherapy or in combination with Vincristine (VCR).

Methods and Results

To determine the anti-leukemic effects of Britannin on ALL-derived cell lines and suggest a mechanism of action for the agent, we used MTT assay, Annexin-V/PI staining, ROS assay, and real-time PCR analysis. Moreover, by using a combination index (CI), we evaluated the synergistic effect of Britannin on Vincristine. We found that unlike normal Peripheral Blood Mononuclear Cells (PBMCs) and L929 cells, Britannin reduced the viability of NALM-6, REH, and JURKAT cells. Among tested cells, NALM-6 cells had the highest sensitivity to Britannin, and this agent was able to induce p21/p27-mediated G1 cell cycle arrest and Reactive Oxygen Specious (ROS)-mediated apoptotic cell death in this cell line. When NALM-6 cells were treated with Nacetyl-L-Cysteine (NAC), a scavenger of ROS, Britannin could induce neither apoptosis nor reduce the survival of the cells suggesting that the cytotoxic effect of Britannin is induced through ROS-dependent manner. Moreover, we found that a low dose of Britannin enhanced the effect of Vincristine in NALM-6 cells by inducing apoptotic cell death via altering the expression of apoptotic-related genes.

Conclusions

Overall, our results proposed a mechanism for the cytotoxic effect of Britannin, either as a single agent or in combination with Vincristine, in NALM-6 cells.

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Acknowledgements

The authors would like to express their gratitude to Shahid Beheshti University of Medical Sciences (Tehran, Iran) for supporting this study and Dr. Aliakbar Mohammadlou, a Postdoctoral researcher at Boston College, who helped with editing the manuscript.

Funding

This study was supported by a fund of Laboratory Hematology and Blood Bank Department, School of Allied Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Department of Laboratory Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hassan Mohammadlou, Mohammad Hossein Mohammadi, Amir Yami & Ahmad Gharehbaghian

  2. Traditional Medicine and Materia Medica Research Center and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maryam Hamzeloo-Moghadam

  3. Pediatric Congenital Hematologic Disorders Research Center, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ahmad Gharehbaghian

  4. HSCT Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Hossein Mohammadi

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  1. Hassan Mohammadlou
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  2. Maryam Hamzeloo-Moghadam
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  3. Mohammad Hossein Mohammadi
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  4. Amir Yami
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  5. Ahmad Gharehbaghian
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Contributions

HM carried out the experiments and drafted the manuscript; MH-M collected I. aucheriana, prepared, isolated, and purified the compound; MHM was involved in supervising the project; AY designed the primers; AG conceived the study, designed and coordinated it, and finalized the manuscript. All authors gave final approval for publication.

Corresponding author

Correspondence to Ahmad Gharehbaghian.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Mohammadlou, H., Hamzeloo-Moghadam, M., Mohammadi, M.H. et al. Britannin, a sesquiterpene lactone induces ROS-dependent apoptosis in NALM-6, REH, and JURKAT cell lines and produces a synergistic effect with vincristine. Mol Biol Rep 48, 6249–6258 (2021). https://doi.org/10.1007/s11033-021-06572-x

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  • DOI: https://doi.org/10.1007/s11033-021-06572-x

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