Pi‐Class Glutathione S‐transferase (GSTP1)‐Selective Fluorescent Probes for Multicolour Imaging with Various Cancer‐Associated Enzymes

Abstract

Pi-class glutathione S-transferase (GSTP1) is highly expressed in a wide variety of human cancer tissues compared to the corresponding normal counterpart. Therefore, GSTP1 is a potential target enzyme for overcoming resistance to chemotherapeutic agents or visualizing specific lesions such as cancer.Here, we present orange and red fluorescence-emitting probes selective for GSTP1. Carbofluorescein and TokyoMagenta fluorophores were modified with a previously described GSTP1selective chromogenic compound to generate orange and red fluorescence probes, respectively. Of these probes, Ps-CF, the orange fluorescence-emitting probe, was confirmed to be highly specific for detecting GSTP1 exogenously or endogenously expressed in various cancer cells. Additionally, it was demonstrated that Ps-CF is applicable for the simultaneous detection of GSTP1 and another cancer-associated enzyme by using a green fluorescence emitting γ-glutamyl transpeptidase (GGT) probe. In conclusion, the fluorescent probes developed in this study enable the simultaneous detection of multiple tumour markers such as GSTP1 with other cancer-associated enzymes by concurrently using spectrally distinguished fluorescent probes, potentially broadening the scope of cancer detection.

Advances and Perspectives of Responsive Probes for Measuring γ-Glutamyl Transpeptidase

“…Previous studies have clearly identified the elevated GGT levels in cancer, e.g., 494.5765 U/L of GGT in HeLa cells, while 5–85 U/L in blood of normal adult . Taking this fact into consideration, GGT has been explored as a potential diagnostic and prognostic biomarker for various cancers …”

“…39 Taking this fact into consideration, GGT has been explored as a potential diagnostic and prognostic biomarker for various cancers. 108 As introduced above, Urano and co-workers developed an "off−on" response fluorescence probe (γGlu-HMRG, Probe #1) for GGT measurement. The GGT could cleave the γglutamyl from γGlu-HMRG to release the fluorescent HMRG that was then rapidly internalized into cells and accumulated primarily in lysosomes to promote the fluorescence specifically in enzyme-expressing cells (Figure 2).…”