Preview

Antibiot Khimioter = Antibiotics and Chemotherapy

Advanced search

Glutoxime, as an Inhibitor of Multiple Drug Resistance Phenotype Associated with Pgp Expression

Abstract

Interaction of Glutoxime with P-glucoprotein (Pgp), a multiple drug resistance marker, as well as the Glutoxime impact on doxorubicin intracellular accumulation were investigated. It was shown that the Glutoxime effect on the Pgp expressing tumor cells resulted in a decrease of the cell specific fluorescence intensity, conditioned by binding of the monoclonal antibodies to the transport protein. That was evident of Glutoxime competition with the monoclonal antibodies for binding to Pgp and indicative of the modificator interaction with the transport protein. The effect was proved with the use of two cultures of human tumor cells of different histogenesis, i. e. the cells of Jurkat T-cellular leukemia and nonsmall cell lung cancer A549. Inhibition of the Pgp functional activity by Glutoxime was also demonstrateds. The authors suggested that it could be caused by direct competition of the modificator with the antitumor agent for binding to the precipitation sites on Pgp. Glutoxime could be considered as an inhibitor of multiple drug resistance associated with the Pgp function.

About the Authors

T. A. Bogush
N. N. Blokhin Russian Scientific Centre of Cancer, Russian Academy of Medical Sciences
Russian Federation


E. A. Dudko
N. N. Blokhin Russian Scientific Centre of Cancer, Russian Academy of Medical Sciences
Russian Federation


E. A. Bogush
N. N. Blokhin Russian Scientific Centre of Cancer, Russian Academy of Medical Sciences
Russian Federation


V. YU. Kirsanov
N. N. Blokhin Russian Scientific Centre of Cancer, Russian Academy of Medical Sciences
Russian Federation


V. G. Antonov
N. N. Blokhin Russian Scientific Centre of Cancer, Russian Academy of Medical Sciences
Russian Federation


References

1. Bogush T., Robert J. Multidrug resistance reversal in solid tumors. ABC transporters and multidrug resistance. WILEY, 2009; 349-362.

2. Filomeni G., Rotilio G., Ciriolo M. R. Cell signalling and the glutathione redox system. Biochem Pharmacol 2002; 64: 1057-1064.

3. Jordan P. A., Gibbins J. M. Extracellular disulfide exchange and the regulation of cellular function. Antioxidants & Redox Signalling 2006; 8: 4: 312-324.

4. Соколова Г. Б., Синицин М. В., Кожемякин Л. А. и др. Глутоксим в комплексной терапии туберкулеза. Антибиотики и химиотер 2002; 47: 2: 20-23.

5. Новиков А. И., Кононов А. В., Охлопков В. А. и др. Эффективность Глутоксима в комплексной терапии больных каплевидной формой псориаза. Росс журн кож вен бол 2003; 1: 38-41.

6. Курилова Л. С., Крутецкая З. И., Лебедев О. Е. и др. Влияние окисленного глутатиона и его фармакологического аналога препарата Глутоксим на внутриклеточную концентрацию Ca2+ в макрофагах. Цитология 2008; 50: 5: 452-460.

7. Крутецкая З. И., Лебедев О. Е., Курилова Л. С. и др. Возможное участие ионов кальция в регуляторном действии окисленного глутатиона на макрофаги. Доклады Академии наук 2007; 412: 5: 1-4.

8. Манихас Г. М., Филатова Е. И., Былинская Е. Н. и др. Применение препарата Глутоксима при сочетанной лучевой терапии местнораспространённого рака шейки матки. Росс онкол журн 2008; 1: 23-28.

9. Богуш Т. А., Дудко Е. А., Богуш Е. А. и др. Характеристика взаимодействия специфических антител с Pgp в клетках Т-лимфобластного лейкоза линии Jurkat. Антибиотики и химиотер 2009; 54: 1-2: 3-9.

10. Богуш Т. А., Равчеева А. Б., Конухова А. В. и др. Новый подход к оценке функциональной активности АВС-транспортеров, контролирующих внутриклеточное распределение противоопухолевых препаратов, методом проточной цитофлюориметрии. Доклады Академии наук 2005; 405: 5: 682-685.


Review

For citations:


Bogush T.A., Dudko E.A., Bogush E.A., Kirsanov V.Yu., Antonov V.G. Glutoxime, as an Inhibitor of Multiple Drug Resistance Phenotype Associated with Pgp Expression. Antibiot Khimioter = Antibiotics and Chemotherapy. 2010;55(5-6):18-23. (In Russ.)

Views: 396


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 0235-2990 (Print)