NO-donating aspirin induces phase II enzymes in vitro and in vivo.

摘要: Modulation of drug metabolizing enzymes, leading to facilitated elimination carcinogens represents a successful strategy for cancer chemoprevention. Nitric oxide-donating aspirin (NO-ASA) is promising agent the prevention colon and other cancers. We studied effect NO-ASA on enzymes in HT-29 human adenocarcinoma Hepa 1c1c7 mouse liver cells Min mice treated with 3 weeks. In these cell lines, induced activity expression NAD(P)H:quinone oxireductase (NQO) glutathione S-transferase (GST). Compared untreated mice, increased (nmol/min/mg; mean+/-SEM all) NQO (85+/-6 versus 128+/-11, P<0.05) GST (2560+/-233 4254+/-608, P<0.005) also intestine but not kidney; NQO1 P1-1 was increased. had only marginal P450 1A1 2E1, two phase I enzymes. The release NO from NO-ASA, determined selective microelectrode paralleled by induction abrogated scavengers; an exogenous donor NQO1. concentration-dependently translocation Nrf2 into nucleus as documented immunofluorescence immunoblotting; this P1-1. Thus induces II at least part, through action that it releases modulating Keap1-Nrf2 pathway; may be part its mechanism against