"Combination Treatments of Imatinib with Astaxanthin and Crocin Efficiently Ameliorate Antioxidant Status, Inflammation and Cell Death Progression in Imatinib-resistant Chronic Myeloid Leukemia Cells"

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2024 Jan 16

PMID 38227060

Authors

Amin Golestani

Atefeh Rahimi

Mahsa Najafzadeh

Mahtab Sayadi

Seyed Mehdi Sajjadi

Affiliations

Soon will be listed here.

Abstract

Background: Imatinib resistance remains a major obstacle in the treatment of chronic myelogenous leukemia (CML). Crocin (CRC) and astaxanthin (ATX) are phytochemicals with anti-cancer properties.

Aims: This study aimed to explore the effects of combination treatment of Imatinib with CRC and ATX on Imatinib-resistant K562 (IR-K562) cells.

Methods And Results: After the establishment of IR-K562 cells, growth inhibitory activity was determined by the MTT assay. To test the regeneration potential, a colony formation assay was performed. Cell cycle analyses were examined by flow cytometry. Cell injury was evaluated by lactate dehydrogenase (LDH) leakage. Real-time PCR was applied to assess the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay. Antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay. After 48 h of treatment, ATX (IC = 30µM) and CRC (IC = 190µM) significantly inhibited cell proliferation and colony formation ability, induced G1 cell cycle arrest and cell injury, upregulated the expression of apoptosis-associated genes, and downregulated the expression of anti-apoptotic and inflammatory genes. The combination of IM with ATX and/or CRC synergistically reduced cell viability (combination index [CI] < 1).

Conclusion: Our data suggest that IM shows better therapeutic efficacy at lower doses when combined with ATX and/or CRC.

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