TY - JOUR
T1 - Reactive Oxygen Species Synergize to Potently and Selectively Induce Cancer Cell Death
AU - Lee, Hyang Yeon
AU - Parkinson, Elizabeth I.
AU - Granchi, Carlotta
AU - Paterni, Ilaria
AU - Panigrahy, Dipak
AU - Seth, Pankaj
AU - Minutolo, Filippo
AU - Hergenrother, Paul J.
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/5/19
Y1 - 2017/5/19
N2 - 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.
AB - 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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U2 - 10.1021/acschembio.7b00015
DO - 10.1021/acschembio.7b00015
M3 - Article
C2 - 28345875
AN - SCOPUS:85019592597
SN - 1554-8929
VL - 12
SP - 1416
EP - 1424
JO - ACS chemical biology
JF - ACS chemical biology
IS - 5
ER -