The objective was to investigate the effect of
4-hydroxybenzoic acid (4-HBA) and
4-hydroxy-3-methoxybenzoic acid (
Vanillic acid, VA) on
p-glycoprotein (P-gp) activity in multidrug-resistant K562/Dox
cancer cells. The cytotoxic and co-treatment with
pirarubicin (Pira) were analyzed using a
resazurin assay. A noninvasive functional spectrofluorometric technique was used to determine the kinetics of Pira uptake in living multidrug-resistant K562/Dox
cancer cells. The three
biological endpoints for determination of cellular energetic state included the activity of mitochondria, mitochondrial membrane potential (ΔΨm), and
ATP levels. The results revealed that
4-HBA (10 mM) and
VA (5 and 10 mM) statistically decreased cell viability in K562 and multidrug-resistant K562/Dox
cancer cells. In ways consistent with that result,
4-HBA and VA (0.01, 0.1, 1, and 10 mM) could statistically decrease the IC50 of Pira in K562 and multidrug-resistant K562/Dox
cancer cells at 48 and 72 h. The overall intracellular Pira concentration increased in 4-HBA- and VA-treated multidrug-resistant K562/Dox
cancer cells when compared to control. The ratio of ka i/ka 0 in 4-HBA- and VA-treated multidrug-resistant K562/Dox
cancer cells was significantly decreased when
4-HBA and VA concentration increased. The activity of mitochondria, ΔΨm, and
ATP levels significantly reduced in multidrug-resistant K562/Dox
cancer cells incubated with 0.01, 0.1, 1, and 10 mM
4-HBA and VA at all harvest time points. In conclusion,
4-HBA and VA were able to bring about cell death in multidrug-resistant K562/Dox
cancer cell at high concentrations. The
4-HBA and VA could modify P-gp function via an impaired cellular energetic state, resulting in increased in intracellular
drug concentration in multidrug-resistant K562/Dox
cancer cells.