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Effects of co-administration of arsenic trioxide and Schiff base oxovanadium complex on the induction of apoptosis in acute promyelocytic leukemia cells

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Abstract

Acute promyelocytic leukaemia (APL) is commonly treated with arsenic trioxide (As2O3) that has many side effects. Given the increasing trend of studies on beneficial therapeutic properties of synthetic compounds containing vanadium, the present study sought to use Schiff base oxovanadium complex to reduce the needed concentration of arsenic trioxide. The HL-60 cell line, which is a model of APL, was selected and the effects of arsenic trioxide and Schiff base oxovanadium complex were individually and simultaneously evaluated on the cell viability by the MTT assay. Flow cytometry and Real-time RT-PCR were also performed to investigate the rate of apoptosis and the expression of P53 and P21 genes, respectively. The IC50 of arsenic trioxide and Schiff base oxovanadium complex on Hl-60 cells was 8.37 ± 0.36 µM and 34.12 ± 1.52 µg/ml, respectively. At the simultaneous administration of both compounds, the maximum decrease in the cell viability was seen in co-administration of 40 µg/ml of Schiff base oxovanadium complex and 0.001 µM of arsenic trioxide. Real-time RT-PCR indicated that the co-administration of Schiff base oxovanadium complex 40 µg/ml and arsenic trioxide 0.001 µM could increase the expression of P53 and P21 genes by 3.76 ± 0.19 and 6.57 ± 1.29 fold change, respectively to the control sample. The flow cytometry studies also indicated that this co-administration could induce apoptosis up to 67% ± 0.9% significantly higher than the control sample. The use of Schiff base oxovanadium complex could significantly reduce the required dose of arsenic trioxide to induce apoptosis in HL-60 cells.

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Acknowledgements

The authors are grateful to the Research Council of Mashhad University of Medical Sciences, Mashhad, Iran, and to the Semnan University of Medical Sciences, Semnan, Iran, for approval and financial support of this project (Grant Nos. 960748, and 1283, respectively). The results described in this paper were of Ms. Sara Mirjalili's master's thesis.

Funding

The authors are grateful to the Research Council of Mashhad University of Medical Sciences, Mashhad, Iran, and to the Semnan University of Medical Sciences, Semnan, Iran, for approval and financial support of this project (Grant Nos. 960748, and 1283, respectively).

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Authors and Affiliations

  1. Biochemistry department, Faculty of Medicine, Semnan University of Medical Sciences, 5th Km Damghan Road, P.O. Box 3514533, Semnan, Iran

    Sara Mirjalili & Ali Khaleghian

  2. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Kalalinia

  3. Dept. Pharmaceutical Biotechnology, School of Pharmacy, P. O. Box 91775-1365, Mashhad, Iran

    Fatemeh Kalalinia

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  1. Sara Mirjalili
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  2. Ali Khaleghian
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  3. Fatemeh Kalalinia
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FK conceived of the study, designed the study, and coordinated and helped to statistical analysis and draft the manuscript. SM carried out the cellular and molecular studies, performed the statistical analysis and drafted the manuscript. AK conceived of the study, participated in its design and drafting of the manuscript.

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Correspondence to Ali Khaleghian or Fatemeh Kalalinia.

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Mirjalili, S., Khaleghian, A. & Kalalinia, F. Effects of co-administration of arsenic trioxide and Schiff base oxovanadium complex on the induction of apoptosis in acute promyelocytic leukemia cells. Biometals 34, 1067–1080 (2021). https://doi.org/10.1007/s10534-021-00330-z

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