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

Dokl Biochem Biophys. 2017 Jan;472(1):27-30. doi: 10.1134/S1607672917010100. Epub 2017 Apr 19.

Abstract

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Apoptosis / drug effects*
  • Cell Hypoxia
  • Deferoxamine / toxicity
  • Doxorubicin / toxicity
  • HCT116 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Siderophores / toxicity
  • Verapamil / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Siderophores
  • Doxorubicin
  • Verapamil
  • Deferoxamine