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

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• 作者：Kamata ; Keiko ; Okamoto ; Shiho ; Oka ; Shin-ichi ; Kamata ; Hideaki ; Yagisawa ; Hitoshi ; Hirata ; Hajime
• 关键词：Cycloprodigiosin ; Nuclear factor κ ; B ; Tumor necrosis factor ; Iκ ; B kinase ; Apoptosis ; Anti-tumor ; cPrG· ; HCl ; cycloprodigiosin hydrochloride ; Iκ ; B ; inhibitor of nuclear factor-κ ; B ; IKK ; inhibitor of nuclear factor-κ ; B kinase ; NF-&#
• 刊名：FEBS Letters
• 出版年：2001
• 出版时间：October 19, 2001
• 年：2001
• 卷：507
• 期：1
• 页码：74-80
• 全文大小：316 K

文摘

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.