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Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens

Kazuhiro Satake1, Megumi Tsukamoto1, Yuji Mitani1

  • 1Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.

Bio-Medical Materials and Engineering
|September 26, 2015
PubMed

Insights

Human ABCB1 (P-glycoprotein) confers multidrug resistance (MDR) by transporting guanidine alkaloids from Pterogyne nitens. This study reveals ABCB1

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Biochemistry

Background:

  • Multidrug resistance (MDR) mediated by human ABCB1 (P-glycoprotein/MDR1) significantly hinders chemotherapy efficacy.
  • Understanding ABCB1's role in MDR is crucial for developing strategies to overcome treatment resistance.

Purpose of the Study:

  • To investigate the mechanism by which ABCB1 confers resistance to four guanidine alkaloids from Pterogyne nitens.
  • To assess the potential of these alkaloids as substrates for ABCB1 and their impact on ABCB1-mediated drug efflux.

Main Methods:

  • Establishment of human ABCB1-expressing cells (Flp-In-293/ABCB1) and control cells (Flp-In-293/Mock).
  • Cytotoxicity assays (MTT) to evaluate the effects of guanidine alkaloids and known ABCB1 substrates (taxol, vinblastine) on cell viability.
  • ATPase assays to determine if the guanidine alkaloids stimulate ABCB1's intrinsic ATPase activity.

Main Results:

  • ABCB1-expressing cells demonstrated resistance to the four guanidine alkaloids, galegine, nitensidine A, pterogynidine, and pterogynine, as well as to taxol and vinblastine, compared to control cells.
  • The four guanidine alkaloids exhibited cytotoxicity against both cell lines, indicating inherent activity.
  • Guanidine alkaloids were found to stimulate the ATPase activity of ABCB1, suggesting they are substrates.

Conclusions:

  • Human ABCB1 confers resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.
  • ABCB1 actively transports these alkaloids, contributing to their reduced efficacy in the presence of ABCB1.
  • These findings provide insights into overcoming MDR mediated by ABCB1 for chemotherapy applications.
Keywords:
ABCB1ATP-binding cassette (ABC) transporterP-glycoproteinguanidine alkaloids

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