Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells

Abstract

Based on these data, we expected that inhibition of Nrf2 could exert dual effects against HCV infection and proliferation of C-HCC. [...]to explore such dual effects by an Nrf2 inhibitor in vitro, we chose the quassinoid, brusatol, a compound derived from a natural product, which has been shown to inhibit the Nrf2 pathway and to reduce tumors in vivo and in vitro [31, 32]. Furthermore, brusatol selectively inhibits the Nrf2 pathway, and the reduction of Nrf2 is through enhancement of ubiquitination and degradation of Nrf2 [31]. [...]the alteration of mRNA expression observed in the present study could be a secondary phenomenon after reduction of Nrf2 protein caused by brusatol. [...]according to the result from the present experiment using the HCV replicon-replicating OR6 cells, inhibition of HCV infection by brusatol is mediated at least via inhibition of HCV replication, which occurs around host lipid droplets [41]. [...]the suppression of HCV infection by brusatol seems to be contradictory to the general concept that Nrf2 promotes host defense against various pathogens. [...]study will be needed to identify the gene responsible for brusatol inhibition of HCV persistence and to clarify the precise mechanism by which brusatol inhibits HCV infection.