Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbital.
Induction of phase 2 enzymes is a major strategy in chemoprotection against cancer. Inducers belong to nine different chemical classes. In this study we found that a measure of the tendency of 30 plant phenylpropenoids and synthetic analogs to release electrons correlates linearly with their potency in inducing the activity of NAD(P)H:quinone reductase (NQO1), a prototypic phase 2 cancer-protective enzyme. The tendency to release electrons was determined by the energy of the highest occupied molecular orbital (E(HOMO)), calculated by simple quantum-mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute E(HOMO) of an agent, A, i.e., the lower its reduction potential, E(A*+/A), the stronger is its electron donor property and the greater its inducer potency. The finding of this redox ranking of the inducers demonstrates the possibility of controlling and predicting the genetic expression of an enzymatic defense against cancer by xenobiotics via one physicochemical parameter, the reduction potential, E(A*+/A).
Zoete
Vincent
V
Laboratoire de Chimie Biophysique, Université Louis Pasteur, ISIS, CNRS UMR 7006, Strasbourg, France.
Rougée
Michel
M
Dinkova-Kostova
Albena T
AT
Talalay
Paul
P
Bensasson
René V
RV
D004790:Enzyme Induction; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D010084:Oxidation-Reduction
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human