Astaxanthin Co-treatment with Low Dose Methotrexate Increases the Cell Cycle Arrest and Ameliorates the Methotrexate-induced Inflammatory Response in NALM-6

Moridi, Nastaran; Najafzadeh, Mahsa; Sayadi, Mahtab; Sajjadi, Seyed Mehdi

doi:10.22088/IJMCM.BUMS.13.2.133

International Journal of Molecular and Cellular Medicine (IJMCM)

Cellular and Molecular Biology Research Center, Babol University of Medical Sciences

Fri, Apr 25, 2025 [Archive]

Volume 13, Issue 2 (Int J Mol Cell Med 2024) Int J Mol Cell Med 2024, 13(2): 133-146 | Back to browse issues page

‎ 10.22088/IJMCM.BUMS.13.2.133

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Moridi N, Najafzadeh M, Sayadi M, Sajjadi S M. Astaxanthin Co-treatment with Low Dose Methotrexate Increases the Cell Cycle Arrest and Ameliorates the Methotrexate-induced Inflammatory Response in NALM-6. Int J Mol Cell Med 2024; 13 (2) :133-146
URL: http://ijmcmed.org/article-1-2287-en.html

Astaxanthin Co-treatment with Low Dose Methotrexate Increases the Cell Cycle Arrest and Ameliorates the Methotrexate-induced Inflammatory Response in NALM-6

Nastaran Moridi¹

, Mahsa Najafzadeh¹

, Mahtab Sayadi²

, Seyed Mehdi Sajjadi³

1- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.
2- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
3- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. , mehdi.sadjadi@bums.ac.ir

Abstract: (677 Views)

Methotrexate (MTX), an antimetabolite agent, is widely used for acute lymphoblastic leukemia treatment, despite its association with significant organ dysfunction. Astaxanthin (AST) is a natural carotenoid which has recently been emerged as a promising anti-tumor and anti-inflammatory agent. In this study, we aimed to evaluate the effectiveness of astaxanthin and low-dose methotrexate co-treatment in acute lymphoblastic leukemia cell line. The expression of Dihydrofolate reductase (DHFR), Thymidylate synthase (TYMS), apoptotic, anti-apoptotic as well as inflammatory genes was investigated using qRT-PCR. Flow cytometry was performed for cell cycle quantitative evaluation. Clonogenic assay was used to assess NALM6 cells proliferation capacity following treatment with AST, MTX, and co-treatment. To compare the antioxidant property of each group, the ferric ion reducing anti-oxidant power assay was performed. A reduction in viability was observed in the presence of MTX, AST, and their combined treatment. Both AST alone and in combination with MTX caused cell cycle arrest and a reduction in the expression of DHFR and TYMS. While MTX, AST, and their combination could reduce STAT3 and BCL-XL gene expression, they could act as positive regulators for the expression of BAX and CASP3, TNFα, and IL6. AST and MTX co-treatment inhibited the colony formation ability. FRAP assay also revealed that AST and AST+MTX increased the antioxidant capacity. Our data suggests that AST can improve MTX treatment efficacy and their combination therapy can be considered as a promising strategy for the management of acute lymphoblastic leukemia.

Keywords: Acute lymphoblastic leukemia, Astaxanthin, Methotrexate, NALM-6

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Type of Study: Original Article | Subject: Cancer
Received: 2024/01/28 | Accepted: 2024/07/7 | Published: 2024/08/6