New Syntrix Publication: Glutathione S-Transferase P1-1 Expression Modulates Sensitivity of Human Kidney 293 Cells to Photodynamic Therapy with Hypericin
Congratulations to Syntrix scientists and collaborators at the University of Washington on their latest publication, which appeared in the journal Archives of Biochemistry and Biophysics.
Title: Glutathione S-transferase P1-1 expression modulates sensitivity of human kidney 293 cells to photodynamic therapy with hypericin. Authors: Dabrowski MJ, Maeda D, Zebala J, Lu WD, Mahajan S, Kavanagh TJ, Atkins WM.
Abstract: Photodynamic therapy (PDT) relies on light-dependent, tissue-targeted, oxidative stress in tumors that have accumulated a photosensitizing drug. Glutathione S-transferases (GSTs) are often up-regulated in tumors and they modulate oxidative stress by several isoformdependent mechanisms. GSTs, therefore, are potential confounding factors in PDT. Therefore, we examined this possibility in human kidney 293 cells transfected with a plasmid encoding either green fluorescent protein alone (pIRES-GFP) or both GFP and GSTP1-1 (pIRES-GFPGSTP). Cells were cultured and treated with light alone, the sensitizer hypericin (HYP) alone, or light and HYP. Cells harboring pIRES-GFP-GSTP exhibited a modest 2-fold increase in GSTP1-1 expression over control cells. On the basis of flow cytometry and microscopy, the light-dependent toxicity of HYP was reduced in cells over-expressing GSTP1-1. Paradoxically, the decreased toxicity in the cells with GSTP1-1 over-expression occurred concomitantly with a modest approximately 2-fold increase in cellular uptake of the drug. Immunoprecipitation of HYP and Western analysis indicated that GSTP1-1 is a major intracellular-binding site for HYP. These results are the first to demonstrate GST expression as a confounding variable of photodynamic therapy. Further, a high-affinity GST inhibitor reversed the GSTP1-1-dependent resistance, suggesting the possible utility of pharmacological strategies to optimize PDT.
Link to paper.