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Astaxanthin decreases the growth-inhibitory dose of cytarabine and inflammatory response in the acute lymphoblastic leukemia cell line NALM-6

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Abstract

Background

In spite of the great progress in acute lymphoblastic leukemia (ALL) treatment, a large number of patients still suffer from chemotherapy drug toxicity. As a routine medication for ALL treatment, cytarabine (Ara-C) has many side effects on the patients. Astaxanthin (ASX), on the other hand, is a carotenoid with antioxidant, anti-inflammatory and anti-cancer properties.

Purpose

The present study investigated the effects of ASX in combination with Ara-C on cell proliferation, apoptosis induction, and cell cycle arrest in NALM-6 cell line.

Methods

NALM6 cells were treated with different concentrations of ASX, Ara-C, and their co-treatment. Cytotoxic effects were evaluated using MTT assay. After treating the cells with the IC50 dose of ASX, Ara-C and their co-treatment, we studied apoptosis induction, cell cycle arrest, and expression of apoptotic, anti-apoptotic, and inflammatory genes.

Result

MTT assay demonstrated that co-treatment of cytarabine and ASX had greater cytotoxicity effects compared with the IC50 dose of Ara-C alone. After 48 h of treatment of NALM-6 cells with the combination dose, expression levels of apoptotic genes (P53, caspase-8, 3), the anti-apoptotic gene (Bcl-xL) and inflammatory genes (IL-6, TNF-α) changed significantly compared to the untreated group (p < 0.05).

Conclusions

Co-treatment of ASX and Ara-C has synergism effects on apoptosis pathways, cell proliferation inhibition, and decreased inflammation.

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Data availability

Not applicable.

Abbreviations

ALL:

Acute lymphoblastic leukemia

Ara-C:

Arabinosyl cytosine

ASX:

Astaxanthin

Caspase:

Cysteine-aspartic acid protease

TNF-α:

Tumor necrosis factor- α

IL-6:

Interleukin-6

Bcl-xL:

B-cell lymphoma-extra-large

DMSO:

Dimethyl sulfoxide

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Acknowledgements

We would like to thank BUMS core research laboratory for providing the facilities for conducting this research.

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Authors and Affiliations

  1. Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran

    Amirhossein Rastgar

  2. Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran

    Mahtab Sayadi, Gholamreza Anani-Sarab & Seyed Mehdi Sajjadi

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  1. Amirhossein Rastgar
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  2. Mahtab Sayadi
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  3. Gholamreza Anani-Sarab
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  4. Seyed Mehdi Sajjadi
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Contributions

AR: Carried out the experiments, wrote the manuscript, and did data analysis. MS (co-first author): designed the study, carried out the experiments, wrote the manuscript, and did data analysis. GAS: Edited the manuscript and did data interpretation. SMS: designed the study, supervised the project, and revised the manuscript.

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Correspondence to Seyed Mehdi Sajjadi.

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Mahtab Sayadi contributed equally to this work as the first author.

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Rastgar, A., Sayadi, M., Anani-Sarab, G. et al. Astaxanthin decreases the growth-inhibitory dose of cytarabine and inflammatory response in the acute lymphoblastic leukemia cell line NALM-6. Mol Biol Rep 49, 6415–6422 (2022). https://doi.org/10.1007/s11033-022-07452-8

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