Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway independently of NF-κB transcription factor

• Autores: Alaniz, L.; García, M.G.; Gallo-Rodriguez, C.; Agusti, R.; Sterín-Speziale, N.; Hajos, S.E.; Alvarez, E.
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Glycobiology 2006;16(5):359-367
• Materia: Akt; Apoptosis; HPAEC-PAD; Hyaluronan oligomers; NF-κB; P13-K; hyaluronic acid; I kappa B alpha; immunoglobulin enhancer binding protein; oligosaccharide; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate; protein kinase B; wortmannin; amperometry; animal cell; anion exchange chromatography; apoptosis; article; cancer cell culture; cell death; cell function; cell survival; controlled study; enzyme activity; enzyme inhibition; enzyme synthesis; hypothesis; inhibition kinetics; lymphoma; mouse; nonhuman; pH; priority journal; protein phosphorylation; signal transduction; 1-Phosphatidylinositol 3-Kinase; Animals; Apoptosis; Cell Death; Cell Line, Tumor; Dose-Response Relationship, Drug; Hyaluronic Acid; Lymphoma; Mice; Molecular Weight; NF-kappa B; Proto-Oncogene Proteins c-akt; Signal Transduction; Animalia
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Several studies indicate that hyaluronan oligosaccharides (oHA) are able to modulate growth and cell survival in solid tumors; however, no studies have been undertaken to analyze the effect of oHA on T-lymphoid disorders. In this work we showed that oHA were able to induce apoptosis in lymphoma cell lines. Since PI3-K/Akt and nuclear factor-κB (NF-κB) are major factors involved in cell survival and anti-apoptotic pathways in lymphoma cells, we hypothesized that oHA could induce apoptosis through inhibition of these pathways. oHA were identified by a method which allows characterization of length using a high pH anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). oHA inhibited PIP3 production (principal product of PI3-K activity) and reduced Akt phosphorylation levels, similarly to the specific inhibitor wortmannin. However, treatment with either oHA or wortmannin failed to inhibit constitutive NF-κB activity and modulate IκBα protein levels, suggesting that PI3-K and NF-κB signaling pathways are not related in the cell lines used. Cell behavior differed using native hyaluronan (HA), which induced PIP3 production, Akt phosphorylation, and NF-κB activation, although not related with cell survival since treatment with native HA showed no effect on apoptosis. Our results suggest that oHA induce apoptosis by suppression of PI3-K/Akt cell survival pathway without involving NF-κB activation, through a mechanism that differs from the one mediated by native HA. © 2006 Oxford University Press.
Fil:Gallo-Rodriguez, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Agusti, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.