Suppression of AP-1 Activity by Cycloprodigiosin Hydrochloride

Abstract

Cycloprodigiosin hydrochloride (cPrG·HCl), a compound isolated from a marine bacterium, acts as an immunosuppressant and an anti-cancer drug. We have previously reported that cPrG·HCl suppressed the transcriptional activation of nuclear factor (NF)-κB. Here we studied the effect of cPrG·HCl on activation of another transcription factor, activator protein 1 (AP-1). cPrG·HCl potently suppressed AP-1 activity induced by tumor necrosis factor (TNF) α and phorbol myristate acetate (PMA). cPrG·HCl did not inhibit any of the mitogen-activated protein kinase (MAPK) families, whereas it did suppress transcriptional activation of AP-1 induced by constitutively activated mutants of MEKK1 or Ras. cPrG·HCl inhibited neither TNFα- or PMA-induced DNA-binding of AP-1 nor co-activator p300-induced activation of AP-1. Taken together, cPrG·HCl suppresses AP-1-dependent gene expression downstream of MAPK group through the inhibition of the transcription activation step of the AP-1 promoter complex.