Inhibition of P-glycoprotein stimulates cell death under Hypoxia-mimicking conditions

The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible fact...

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Bibliographic Details
Published in:Doklady. Biochemistry and biophysics 2017, Vol.472 (1), p.27-30
Main Authors: Vdovin, A. S., Maximchik, P. V., Kulikov, A. V., Zhivotovsky, B. D., Gogvadze, V. G.
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biophysics
Cell death
Cell Hypoxia
Deferoxamine - toxicity
Doxorubicin - toxicity
Drug resistance
Glycoproteins
HCT116 Cells
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Life Sciences
Medicin och hälsovetenskap
Molecular Biology
Siderophores - toxicity
Verapamil - pharmacology
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Summary:The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF-1α) stabilization and inhibition of doxorubicin-induced apoptosis in colon cancer НСТ116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation leading to cell death induction. Considering these results, P-gp may be used as a potential target to stimulate chemotherapeutic drugs activity that will contribute to more efficient tumor cells elimination.
ISSN:1607-6729
1608-3091
1608-3091
DOI:10.1134/S1607672917010100