γ-Glutamyl transpeptidase-activated indole-quinolinium based cyanine as a fluorescence turn-on nucleolus-targeting probe for cancer cell detection and inhibition.

Abstract

A nucleolus as a prominent sub-nuclear, membraneless organelle plays a crucial role in ribosome biogenesis, which is in the major metabolic demand in a proliferating cell, especially in aggressive malignancies. We develop a γ-glutamyltranspeptidase (GGT)-activatable indole-quinolinium (QI) based cyanine consisting of a novel tripeptide fragment (Pro-Gly-Glu), namely QI-PG-Glu as a turn-on red fluorescent probe for the rapid detection of GGT-overexpressed A549 cancer cells in vivo. QI-PG-Glu can be triggered by GGT to rapidly release an activated fluorophore, namely HQI, in two steps including the cleavage of the γ-glutamyl group recognized by GGT and the rapid self-driven cyclization of the Pro-Gly linker. HQI exhibits dramatically red fluorescence upon binding to rRNA for imaging of nucleolus in live A549 cells. HQI also intervenes in rRNA biogenesis by declining the RNA Polymerase I transcription, thus resulting in cell apoptosis via a p53 dependent signaling pathway. Our findings may provide an alternative avenue to develop multifunctional cancer cell-specific nucleolus-targeting fluorescent probes with potential anti-cancer effects.

• Authors: Huanxin Xue, Jiaye Lu, Hongwei Yan, Ju Huang, Hai-Bin Luo, Man Shing Wong, Yuqi Gao, Xiaolei Zhang, Lei Guo
• Journal: Talanta (Talanta) Vol. 237 Pg. 122898 (Jan 15 2022) ISSN: 1873-3573 [Electronic] Netherlands
• PMID: 34736714 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Fluorescent Dyes
• Indoles
• Quinolines
• gamma-Glutamyltransferase

Topics

• Fluorescence
• Fluorescent Dyes
• Indoles
• Neoplasms (diagnostic imaging)
• Quinolines (pharmacology)
• gamma-Glutamyltransferase