Cancer-Specific Biomarker hNQO1-Activatable Fluorescent Probe for Imaging Cancer Cells In Vitro and In Vivo.

Surendra Punganuru,Viswanath Arutla,Hanumantha Madala,Kalkunte Srivenugopal

doi:10.3390/cancers10120470

Cancer-Specific Biomarker hNQO1-Activatable Fluorescent Probe for Imaging Cancer Cells In Vitro and In Vivo.

Surendra Punganuru, Viswanath Arutla + Show 2 more

Open Access

https://doi.org/10.3390/cancers10120470

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Abstract

Human NAD(P)H quinone oxidoreductase-1 (hNQO1) is an important cancer-related biomarker, which shows significant overexpression in malignant cells. Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management. In the present study, we report a new dicyanoisophorone (DCP) based fluorescent probe (NQ-DCP) capable of monitoring hNQO1 activity in vitro and in vivo in both ratiometric and turn-on model. NQ-DCP was prepared by conjugating dicyanoisophorone fluoroprobe with hNQO1 activatable quinone propionic acid (QPA), which remain non-fluorescent until activation by tumor-specific hNQO1. NQ-DCP featured a large Stokes shift (145 nm), excellent biocompatibility, cell permeability, and selectivity towards hNQO1 allowed to differentiate cancer cells from healthy cells. We have successfully employed NQ-DCP to monitor non-invasive endogenous hNQO1 activity in brain tumor cells in vitro and in xenografted tumors developed in nude mice.

Highlights

Human NAD(P)H quinone oxidoreductase-1, formerly referred to as DT diaphorase, is a cytosolic flavoenzyme that plays an essential role in cellular protection against endogenous quinones [1]
NQO1 is expressed in many human solid tumors at levels of 200-fold above that in normal tissue and its elevated activity has been closely associated with tumor progression, aggressiveness, resistance to chemotherapy, and poor prognosis [4,5,6,7,8,9,10,11,12]
The results indicated that reaction product exhibited chromatographic in presence of Human NAD(P)H quinone oxidoreductase-1 (hNQO1) was monitored analysis by incubating peaks at

Summary

Introduction

Human NAD(P)H quinone oxidoreductase-1 (hNQO1), formerly referred to as DT diaphorase, is a cytosolic flavoenzyme that plays an essential role in cellular protection against endogenous quinones (e.g., the vitamin E α-tocopherol quinone, menadione, benzene quinones) [1]. It is a homodimer which binds quinones with the co-factor NADH or NADPH, leading to a reduction of the quinones in a two-electron transfer reaction [2]. HNQO1 has been recognized as a potential biomarker of human malignancies, accurate detection of which can be highly desirable to improve diagnostic efficacy and predict drug responsiveness [13]

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Discussion

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