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

Hyang Yeon Lee, Elizabeth I. Parkinson, Carlotta Granchi, Ilaria Paterni, Dipak Panigrahy, Pankaj Seth, Filippo Minutolo, Paul J. Hergenrother

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1416-1424
Number of pages9
JournalACS chemical biology
Volume12
Issue number5
DOIs
StatePublished - May 19 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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  • Cite this

    Lee, H. Y., Parkinson, E. I., Granchi, C., Paterni, I., Panigrahy, D., Seth, P., Minutolo, F., & Hergenrother, P. J. (2017). Reactive Oxygen Species Synergize to Potently and Selectively Induce Cancer Cell Death. ACS chemical biology, 12(5), 1416-1424. https://doi.org/10.1021/acschembio.7b00015