Research Article Open Access

Diatrizoate, Iopromide and Iotrolan Enhanced Cytotoxicity of Daunorubicin in Multidrug Resistant K562/adr Cells: Impaired the Mitochondrial and Inhibited the P-Glycoprotein Function

Nitaya Snitwongse Na Ayudhya and Samlee Mankhetkorn

Abstract

Multidrug resistance was an obstacle in cancer chemotherapy because the cells decreased their intracellular drug accumulation by energy-dependent compounds efflux pumps such as P-glycoprotein (P-gp). This study observed some iodinated radiographic contrast media, diatrizoate, iopromide and iotrolan affected the cellular energetic state and the kinetics of P-gp in drug-sensitive K562 and drug resistant K562/adr cell lines using spectrophotometer and spectrofluorometer. By colorimetric MTT assay, it was found that contrast media (0-3500 μM) had no effect on both K562 and K562/adr cell viabilities, but in co-treatment with daunorubicin (DNR), diatrizoate decreased cell viability in K562/adr cells by decreasing ICso of DNR from 610.7 ±74.5 nM to 360±108.9 nM. The change in cellular energetic state was studied using rhodamine B as a probe to estimate mitochondrial membrane potential (ΔΨm). The results showed that 3500 μM diatrizoate decreased ΔΨm from 162.2±0.3 mV to 86.9±9.9 mV in K562/adr cells. The kinetics of P-gp-mediated efflux of DNR could be reduced by diatrizoate from 0 (no inhibition) to 0.65±0.11. This inhibition could be partially prevented in co-incubation with 20 nM concanamycin A or 10 μM cytochalasin B. Among the three molecules, diatrizoate showed the best efficiency. It could be proposed for further studies that diatrizoate could be used as MDR identification or MDR imaging and also acted as MDR sensitizing agent in cancer treatments.

American Journal of Applied Sciences
Volume 6 No. 3, 2009, 484-491

DOI: https://doi.org/10.3844/ajassp.2009.484.491

Submitted On: 7 June 2008 Published On: 31 March 2009

How to Cite: Ayudhya, N. S. N. & Mankhetkorn, S. (2009). Diatrizoate, Iopromide and Iotrolan Enhanced Cytotoxicity of Daunorubicin in Multidrug Resistant K562/adr Cells: Impaired the Mitochondrial and Inhibited the P-Glycoprotein Function . American Journal of Applied Sciences, 6(3), 484-491. https://doi.org/10.3844/ajassp.2009.484.491

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Keywords

  • Contrast media
  • Multi Drug-Resistance (MDR)
  • mitochondrial membrane potential (ΔΨm)
  • P-glycoprotein-mediated efflux