Design and Development of an HBT-Based Ratiometric Fluorescent Probe to Monitor Stress-Induced Premature Senescence.

ABSTRACT: Stress-induced premature senescence (SIPS) can be induced in tumor cells by reactive oxygen species (ROS) or oncogenes. The antineoplastic drugs cause apoptosis and senescence by damaging the DNA. Although the detection of cellular senescence is important to monitor drug response during anticancer therapy, only a few probes have been studied for imaging SIPS. In this study, we developed 2-(2'-hydroxyphenyl)benzothiazole (HBT)-based fluorescent probes to determine SIPS by monitoring the oxidative stress and ?-galactosidase activity. HBT is a commonly used fluorophore because of its luminescence mechanism via excited-state intramolecular proton transfer, and it has attractive properties, such as a four-level photochemical process and large Stokes shift (151 nm). A novel fluorescent probe, (2-(benzo[d]thiazol-2-yl)phenyl)boronic acid, was prepared for the detection of ROS, including H2O2, via the oxidation reaction of arylboronic acids to form the fluorescent phenol, HBT. In addition, to determine the enzymatic activity of ?-galactosidase, a 2-(4'-chloro-2'-hydroxyphenyl)benzothiazole (CBT)-based enzymatic turn-on probe (CBT-?-Gal) was designed and synthesized. ?-Galactosidase catalyzed the hydrolysis of ?-galactopyranoside from CBT-?-Gal to release the fluorescent CBT. These probes were capable of ratiometric imaging the accumulation of H2O2 and the degree of ?-galatosidase activity in contrast to H2O2-untreated and H2O2-treated HeLa cells. Furthermore, these probes were successfully employed for imaging the increased levels of ROS and ?-galactosidase activity in the doxorubicin-treated HeLa cells.

SUBMITTER: Makau JN 

PROVIDER: S-EPMC7254510 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature