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

摘要

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 NFkappaB 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 NFkappaB 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 NFkappaB activation is blocked by these products. Our results showed that both tested products substantially inhibited the activation of NFkappaB-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 IkappaBalpha and its induced degradation by Tax. However, both products did not interfere in the nuclear transport of Tax or NFkappaB proteins.