Cycloprodigiosin hydrocloride suppresses tumor necrosis factor (TNF) α‐induced transcriptional activation by NF‐κB

Abstract

Cycloprodigiosin hydrochloride (cPrG·HCl) obtained from a marine bacterium Pseudoalteromonas denitrificans induces apoptotic cell death in various cancerous cell lines. cPrG·HCl alone caused a little cytotoxicity in HeLa cells, but it enhanced the apoptotic process progressively when co‐administered with tumor necrosis factor (TNF)α. Here we studied the effect of cPrG·HCl on TNFα‐induced activation of the transcription factor nuclear factor κB (NF‐κB). Luciferase gene reporter assays revealed that cPrG·HCl potently suppressed the TNFα‐ and the phorbol myristate acetate‐induced activation of NF‐κB. The suppression occurred in the presence of imidazole, indicating that it was not related to the intracellular acidification resulting from the intrinsic H + /Cl − symporter activity of cPrG·HCl. cPrG·HCl inhibited neither the TNFα‐induced phosphorylation and degradation of inhibitor of nuclear factor‐κB, nor the subsequent nuclear translocation and DNA binding of NF‐κB. cPrG·HCl also suppressed NF‐κB‐enhanced gene expression induced by Rac1, Cdc42, MEKK1, inhibitor of nuclear factor‐κα (IKKα), IKKβ, and a subunit of NF‐κB, p65. These results indicate that cPrG·HCl suppresses NF‐κB‐dependent gene expression through the inhibition of transcriptional activation.