Physicochemical properties of phenol and flavone derivatives correlated with their efficacy as inducers of a cancer-protective enzyme and as inhibitors of carcinogenesis in rodents

4^th World Congress on Cancer Science & Therapy

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

René V Bensasson

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

Our investigations establish linear correlations between the ionization potential of exogenous phenol (P) and flavone (F) derivatives and their biological effects on induction of a powerful cancer-protective enzyme NAD(P)H:quinone reductase (NQO1) via the Nrf2-Keap1 pathway. They also show that the NQO1 activation involves (i) oxidation of the P and F inducers to oxidant species which are their quinone derivatives (Q) and (ii) oxidation by these quinones Q of two highly reactive thiol groups of a protein Keap1 activating transcription factor Nrf2. The linear correlations observed for beneficial cancerprotective pathways triggered by electrophiles Q in vitro explain the linear correlations which we observe in vivo (rodents) for the inhibition of chemically-induced carcinogenesis by P and F derivatives. Our in silico evaluation of biological activity of P and F derivatives should orient the rational design of new congeners with greater potency for cancer chemoprotection and might reduce the expensive use of in vivo and in vitro bioassays.