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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 IC 50 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 k a i /k a 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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

4-Hydroxybenzoic acids (4-HBA) and 4-hydroxy-3-methoxybenzoic acid (Vanillic acid, VA) have exhibited several pharmacological activities. Generally, the biological activities of compounds are highly involved in the interaction between protein and compounds in blood plasma. The objective was to investigate the interaction of 4-HBA or VA with human serum albumin (HSA) and their anti-proliferation properties on doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells. The protein binding of 4-HBA or VA to HSA was investigated using fluorescence quenching at temperatures of 298 and 310 Kelvin (K) under the pH of 6.0, 7.4, and 8.0 conditions. The effect of 4-HBA and VA on anti-proliferation was also studied on doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells using resazurin assay. The results showed that 4-HBA and VA could interact with HSA. The fluorescence quenching process in HSA-4-HBA system might be attributed to static quenching mechanism. In contrast, a dynamic quenching mechanism might be mainly involved in the fluorescence quenching process in the HSA-VA system. Thermodynamic data suggested that the spontaneous interaction between HSA and 4-HBA or VA had occurred in the system and it also indicated that hydrogen bonds and Van der Waals forces contributed to the binding of HSA to 4-HBA or VA. In addition, 4-HBA and VA decreased K562 and K562/Dox cells viability in a dose- and time-dependence manner. In conclusions, the 4-HBA and VA could interact with HSA. In addition, the 4-HBA and VA decreased in cell viability for both doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells in a dose- and time-dependence manner. Therefore, these current studies could provide useful information about the nature of 4-HBA or VA binding to protein HSA and their anticancer activities in both of these types of leukemia cells. The cell death mechanisms should be investigated through future study., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

This study reveals the antioxidant properties of iodinated radiographic contrast media to be used in diagnostic radiology. Di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), ferric reducing ability of plasma (FRAP), and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) assays were used for determining in vitro the antioxidant properties of five iodinated radiographic contrast media such as iobitridol (xenetix), iodixanol (visipaque), iohexol (omnipaque), ioxaglate (hexabrix), and isovue (iopamiro). An ascorbic acid and Trolox solution served as a positive control. The absorbance intensity of the colored product was recorded using a spectrophotometer. For DPPH and ABTS assay, the absorbance intensity at 533 and 752 nm, respectively was decreased when compared to control; it indicated an increase in antioxidant activity. For FRAP assay, the absorbance intensity at 593 nm was increased when compared to control; it indicated an increase in antioxidant activity. The results showed that five iodinated radiographic contrast media did not differ in DPPH • radical-scavenging activity when compared to a corresponding control. The ferric reducing ability of all of these iodinated radiographic contrast media also did not differ when compared to a corresponding control, except for iobitridol at 200 mgI/mL and ioxaglate at 50-200 mgI/mL. All iodinated radiographic contrast media showed ABTS •+ radical-scavenging activity. This finding suggested that iobitridol, iodixanol, iohexol, ioxaglate, and isovue exhibited weak in vitro antioxidant properties. The antioxidant ability depended on the type of free radical production and the concentration of iodinated radiographic contrast media.