title: Effect of propolis and caffeic acid phenethyl ester (CAPE) on NFκB activation by HTLV-1 Tax.
abstract: 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 NFκB 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 NFκB 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 NFκB activation is blocked by these products. Our results showed that both tested products substantially inhibited the activation of NFκB-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 IκBα and its induced degradation by Tax. However, both products did not interfere in the nuclear transport of Tax or NFκB proteins.
authors: Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
authors: Jenny
authors: J
authors: Shvarzbeyn
authors: Mahmoud
authors: M
authors: Huleihel
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology*; D015490:HTLV-I Infections / Q000235:genetics* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011429:Propolis / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D044966:Anti-Retroviral Agents; D002109:Caffeic Acids; D016356:Gene Products, tax; D016328:NF-kappa B; C514970:tax protein, Human T-lymphotrophic virus 1; D011429:Propolis; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol