Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3k-Nrf2 signaling

TLDR: In this article, the authors found capsaicin induced expression of heme oxygenase-1 (HO-1) in HepG2 cells and increased the production of reactive oxygen species (ROS).

Abstract: AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 1260 Capsaicin ( trans -8-methyl- N -vanillyl-6-nonenamide), a major pungent ingredient of red pepper, is reported to have anti-mutagenic and anti-carcinogenic properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found capsaicin induced expression of heme oxygenase-1 (HO-1) in HepG2 cells. Capsaicin treatment resulted in a transient increase in the phosphorylation of Akt and subsequently nuclear translocation of NF-E2-related factor 2 (Nrf2) and its binding to antioxidant response element (ARE). HepG2 cells treated with capsaicin exhibited increased production of reactive oxygen species (ROS). Prior exposure of cells with N -acetyl-L-cysteine (NAC) not only blocked the ROS production but also the Akt phosphorylation, nuclear translocation of Nrf2 and Nrf2-ARE binding, as well as HO-1 induction. Moreover, immunoblot analysis showed that while the level of HO-1 protein was elevated, that of NAD(P)H:quinone oxidoreductase (NQO1) was decreased with capsaicin or the inhibitor of NQO1, dicumarol. These results suggested that generation of reactive quinone metabolites of capsaicin that may bind covalently to NQO1 and thereby inhibit its activity may have been responsible for the overproduction of ROS. This, in turn, triggers the phosphorylation of Akt, increases the nuclear translocation of Nrf2 and its binding to ARE and upregulates the expression of HO-1.