Reactive Oxygen Species Synergize To Potently and Selectively Induce Cancer Cell Death

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2017 Mar 28

PMID 28345875

Citations 9

Authors

Hyang Yeon Lee

Elizabeth I Parkinson

Carlotta Granchi

Ilaria Paterni

Dipak Panigrahy

Pankaj Seth

Filippo Minutolo

Paul J Hergenrother

Affiliations

Soon will be listed here.

Abstract

A distinctive feature of cancer cells is their elevated levels of reactive oxygen species (ROS), a trait that can cause cancer cells to be more sensitive to ROS-inducing agents than normal cells. ROS take several forms, each with different reactivity and downstream consequence. Here we show that simultaneous generation of superoxide and hydrogen peroxide within cancer cells results in significant synergy, potently and selectively causing cancer cell death. In these experiments superoxide is generated using the NAD(P)H quinone oxidoreductase 1 (NQO1) substrate deoxynyboquinone (DNQ), and hydrogen peroxide is generated using the lactate dehydrogenase A (LDH-A) inhibitor NHI-Glc-2. This combination reduces tumor burden and prolongs survival in a mouse model of lung cancer. These data suggest that simultaneous induction of superoxide and hydrogen peroxide can be a powerful and selective anticancer strategy.

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