Imatinib Combo Enhances Antioxidant Defense in Leukemia Cells

Imatinib (IM) resistance poses a significant challenge in chronic myelogenous leukemia (CML) treatment. Phytochemicals like crocin (CRC) and astaxanthin (ATX) exhibit anti-cancer properties. Amin Golestani and his team aimed to investigate the impact of combining IM with CRC and ATX on Imatinib-resistant (IR) K562 (IR-K562) cells.

They performed an inclusive analysis after establishing IR K562 cells. Growth inhibitory activity was assessed using the MTT assay, while the regeneration potential was tested through a colony formation assay. Cell cycle analyses were conducted via flow cytometry, and cell injury was evaluated by lactate dehydrogenase (LDH) leakage.

Real-time PCR measured the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay, and antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay.

After 48 hours of treatment, ATX at an (IC50 of 30µM) and CRC (IC50 = 190µM) significantly inhibited cell proliferation and colony formation ability. They 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).

The study concluded that IM exhibits improved therapeutic efficacy at lower doses when combined with ATX and/or CRC.

Source: https://pubmed.ncbi.nlm.nih.gov/38227060/

Golestani A, Rahimi A, Najafzadeh M, et al. (2024). “Combination treatments of imatinib with astaxanthin and crocin efficiently ameliorate antioxidant status, inflammation and cell death progression in imatinib-resistant chronic myeloid leukemia cells”. Mol Biol Rep. 2024 Jan 16;51(1):108. doi: 10.1007/s11033-023-09135-4. PMID: 38227060.