Effect of propolis and caffeic acid phenethyl ester (CAPE) on NFκB activation by HTLV-1 Tax

HTLV-1 is the etiological agent of aggressive malignancy of the CD4(+) T-cells, adult T-cell leukemia (ATL), and other severe clinical disorders. The viral Tax protein is a key factor in HTLV-1 pathogenicity. A major part of Tax oncogenic potential is accounted for by its capacity of inducing the transcriptional activity of the NF kappa B factors, which regulate the expression of numerous cellular genes. Propolis (PE), a natural product produced by honeybees, has been used for a long time in folk medicine. One of PE active components, caffeic acid phenylethyl ester (CAPE), was well characterized and found to be a potent inhibitor of NF kappa B activation. Therefore, the aim of this study was to pursue the possibility of blocking Tax oncogenic effects by treatment with these natural products. Human T-cell lines were used in this study since these cells are the main targets of HTLV-1 infections. We tried to determine which step of Tax-induced NF kappa B activation is blocked by these products. Our results showed that both tested products substantially inhibited the activation of NF kappa B-dependent promoter by Tax. However, only PE could efficiently inhibit also the Tax-induced activation of SRF- and CREB-dependent promoters. Our results showed also that PE and CAPE strongly prevented both Tax binding to I kappa B alpha and its induced degradation by Tax. However, both products did not interfere in the nuclear transport of Tax or NF kappa B proteins. (C) 2011 Elsevier B.V. All rights reserved.