The effects of low-dose X-ray pre-irradiation followed by 4-hydroxybenzoic acid and vanillic acid on P-glycoprotein-mediated efflux pirarubicin in multidrug-resistant K562/Dox cells.

Ohnmar Myint, Benjamaporn Supawat, Suchart Kothan, Montree Tungjai

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Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 authors.

Ohnmar MyintCenter of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 50200, Chiang Mai, Thailand.

Benjamaporn SupawatCenter of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 50200, Chiang Mai, Thailand.

Suchart KothanCenter of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 50200, Chiang Mai, Thailand.

Montree TungjaiCenter of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 50200, Chiang Mai, Thailand. montree.t@cmu.ac.th.

Funding

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6 · The paper itself

Abstract

Leukemia is a hematologic malignancy commonly treated with chemotherapy. However, P-glycoprotein (P-gp)-mediated drug resistance remains a major barrier to effective treatment. To investigate the effects of pre-irradiated with low-dose radiation (LDR) followed by 4-hydroxybenzoic acid (4-HBA) and vanillic acid (VA) treatments on P-gp-mediated efflux pirarubicin (Pira) in living multidrug-resistant K562/Dox cells. Cells were exposed to X-rays at total radiation doses of 0, 0.02, 0.05, and 0.1 Gy. At 24 h following irradiation, 4-HBA and VA (5 and 10 mM) were added to the irradiated cells. The cell viability was assessed at 48 h after irradiation, and succinate dehydrogenase (SDH) activity, mitochondrial membrane potential (ΔΨm), and adenosine triphosphate (ATP) levels were examined at 28 h after irradiation. In addition, the functioning of P-gp-mediated efflux Pira was investigated in living multidrug-resistant K562/Dox cells at 28 h after irradiation. Pre-exposure to LDR followed by 4-HBA and VA treatment significantly decreased cell viability in K562 cells and K562/dox cells when compared to the control. Similarly, pre-exposure to LDR followed by 4-HBA and VA treatment in K562 and K562/Dox cells significantly decreased SDH activity. Additionally, |ΔΨm| and % ATP values had changed when compared to the control. Furthermore, pre-exposure to LDR following treatment with 4-HBA and VA in K562/Dox cells increased the inhibition functioning of P-gp. 4-HBA and VA non-competitively inhibited the P-gp-mediated efflux of Pira. Pre-exposure to LDR followed by 4-HBA and VA treatment could provoke the impairment of energetic state in K562 and K562/Dox cells and also decreases P-gp function in K562/Dox cells.

Indexed as

Antineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1DoxorubicinParabensVanillic AcidAdenosine TriphosphateCell SurvivalDrug Resistance, MultipleDrug Resistance, NeoplasmHumansK562 CellsMembrane Potential, MitochondrialSuccinate DehydrogenaseX-Rays4-hydroxybenzoic acidAdenosine TriphosphateAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1DoxorubicinParabenspirarubicinSuccinate DehydrogenaseVanillic Acid4-Hydroxybenzoic acidCancerLeukemiaMultidrug-resistantRadiationVanillic acid

Identifiers

PMID41772163

DOI10.1007/s00210-026-05150-x

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