The role of GSTπ isoform in the cells signalling and anticancer therapy

M Ściskalska1, H Milnerowicz

  • 1Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland. milena.sciskalska@umed.wroc.pl.

Abstract

Insights

Glutathione S-transferases pi (GST-π) overexpression in cancer cells hinders chemotherapy by promoting drug efflux. Targeting GST-π offers a promising strategy for developing new anticancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Biology

Background:

  • Glutathione S-transferases (GSTs) are overexpressed in chemotherapy-resistant, hyperproliferating tumor cells.
  • Increased GST-π activity enhances drug efflux, reducing the efficacy of anti-cancer treatments.

Purpose of the Study:

  • To review the physiological role of GSTs, particularly GST-π, in cellular signaling and homeostasis.
  • To explore GST-π as a therapeutic target for anticancer strategies and its clinical implications.

Main Methods:

  • Literature review of GSTs' physiological roles.
  • Analysis of GST-π's involvement in key signaling pathways.
  • Examination of GST-π's interaction with therapeutic agents and drug resistance mechanisms.

Main Results:

  • GST-π inactivates MAP kinase pathways, affecting apoptosis.
  • GST-π modulates lipid mediator metabolism and receptor binding, influencing apoptosis.
  • GST-π impacts signal transducer and activator of transcription 3 (STAT3) phosphorylation and growth factor signaling.
  • Inhibition of multidrug resistance-associated protein 1 (MRP-1) can inhibit GST-π activity.

Conclusions:

  • GST-π is a significant target for novel anticancer drug design.
  • Drugs designed to be GST-π substrates or inhibitors can enhance therapeutic outcomes by overcoming drug resistance.

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