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Leukemia is a common malignancy affecting humans worldwide. Pirarubicin (Pira) is one of the anticancer agents used for the treatment of leukemia. Although Pira is effective, drug resistance may develop in cancer cells exposed to this drug, whereas the combination of natural products with Pira may help to overcome this problem. The aim of the present study was to focus on the effect of gallic acid (GA) on the anticancer activity of Pira in K562 leukemia cells and K562/doxorubicin (Dox)-resistant leukemia cells in order to investigate the possible underlying mechanisms. The cell viability, mitochondrial activity, mitochondrial membrane potential (ΔΨm) and ATP levels were assessed in living K562 and K562/Dox cancer cells following treatment with GA/Pira combination, GA alone or Pira alone. P-glycoprotein-mediated efflux of Pira was determined in GA-treated K562/Dox cancer cells. The results demonstrated that GA/Pira combination decreased cell viability, mitochondrial activity, ΔΨm and ATP levels in K562 and K562/Dox cancer cells in a GA concentration-dependent manner compared with non-treated or Pira-treated cells. GA inhibited P-glycoprotein-mediated efflux of Pira in GA-treated K562/Dox cancer cells. Therefore, GA enhanced the anticancer effect of Pira on K562 and K562/Dox cancer cells through cellular energy status impairment, and was able to reverse drug resistance in living K562/Dox cancer cells by inhibiting the function of P-glycoprotein.

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Background: Low-dose X-ray in medical use for diagnosis and therapy can result in cellular biology either directly or indirectly. In cell biology, the interaction of low-dose radiation generates many radical molecules that interact with cellular organelles, such as the plasma membrane. Objectives: This study aimed to evaluate the effect of low-dose X-ray on both drug-sensitive (K562) and drug-resistant (K562/adr) erythroleukemic cell lines. Materials and methods: Cells were exposed by using an X-ray at 135 kVp to obtain the absorbed dose of 0.05, 0.1, and 0.2 Gy. The intracellular reactive oxidant species (RS), malondialdehyde, membrane fluidity, drug uptake, and drug accumulation were instantly observed after radiation. Results: The result showed a significant increase in RS in both cell lines as a function of radiation dose. In K562, the malondialdehyde (MDA) value increased in a radiation dose manner, while membrane fluidity was significantly modified at 0.1 and 0.2 Gy. In K562/adr, the uptake rate of pirarubicin (THP) and IC20 were altered but not significantly different from sham control. Conclusion: Low-dose X-ray significantly increased the intracellular RS in both cell lines and decreased the membrane fluidity at 0.1 Gy of K562. There are alterations of anticancer drug uptake rate in both cell lines, but they are not significant.