TY - JOUR
T1 - Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbital
AU - Zoete, Vincent
AU - Rougée, Michel
AU - Dinkova-Kostova, Albena T.
AU - Talalay, Paul
AU - Bensasson, René V.
PY - 2004/6/1
Y1 - 2004/6/1
N2 - 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 (EHOMO), calculated by simple quantum-mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute EHOMO 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).
AB - 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 (EHOMO), calculated by simple quantum-mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute EHOMO 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).
KW - AM1
KW - Cancer chemoprevention
KW - Cancer chemoprotection
KW - Energy of the highest occupied molecular orbital
KW - Free radicals
KW - Induction of phase 2 enzymes
KW - NAD(P)H:quinone oxidoreductase, NQO1
KW - Plant phenylpropenoids
KW - Redox ranking
KW - Redox regulation
UR - http://www.scopus.com/inward/record.url?scp=2342598377&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2004.03.008
DO - 10.1016/j.freeradbiomed.2004.03.008
M3 - Article
C2 - 15135178
AN - SCOPUS:2342598377
VL - 36
SP - 1418
EP - 1423
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 11
ER -
