The fungal metabolite galiellalactone interferes with the nuclear import of NF-kappa B and inhibits HIV-1 replication

作者：Perez Moises; Soler Torronteras Rafael; Collado Juan A; Limones Carmen G; Hellsten Rebecka; Johansson Martin; Sterner Olov; Bjartell Anders; Calzado Marco A; Munoz Eduardo^*

来源：Chemico-Biological Interactions, 2014, 214: 69-76.

DOI：10.1016/j.cbi.2014.02.012

• Galiellalactone
• HIV-1
• LTR
• NF-kappa B
• Importins

Galiellalactone (GL) is a metabolite produced by the fungus Galiella rufa that presents antitumor and immunomodulatory activities. GL interferes with the binding to DNA of signal transducer and activator of transcription (STAT)-3 and also inhibits other signal pathways such as NF-kappa B, but the mechanism of action in this pathway remains unknown. In this study we report that GL inhibits vesicular stomatitis virus-recombinant HIV-1 infection and the NF-kappa B-dependent transcriptional activity of the HIV-LTR promoter. We found that GL prevents the binding of NF-kappa B to DNA but neither affects the phosphorylation and degradation of NF-KB inhibitory protein, I kappa B alpha, nor the phosphorylation and acetylation of the NF-KB p65 subunit. However, GL prevents the association of p65 with the importin alpha 3 impairing the nuclear translocation of this transcription factor. Using a biotinylated probe we found that GL binds to p65 but not to importin a3. Therefore, GL is a dual NF-kappa B/STAT3 inhibitor that could serve as a lead compound for the development of novel drugs against HIV-1, cancer and inflammatory diseases.

• 出版日期2014-5-5