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

ALANIZ LAURA; GARCÍA MARIANA; GALLO-RODRIGUEZ CAROLA; AGUSTI ROSALÍA; STERÍN-SPEZIALE NORMA B; HAJOS SILVIA E; ALVAREZ ELIDA

GLYCOBIOLOGY

Oxford University Press

Lugar: Oxford OX2 6DP; Año: 2006 vol. 16 p. 359 - 367

0959-6658

Abstract Several studies indicate that hyaluronan (HA) oligosaccharides are able to modulate growth and cell survival in solid tumors, however, no studies have been undertaken to analyze the effect of HA oligosaccharides (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 NFkB are major factors involved in cell survival and anti-apoptotic pathways in lymphoma cells, we hypothesized that oHA could induce apoptosis trough 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 NFkB activity and modulate IkBa protein levels, suggesting that PI3-K and NFkB signaling pathways are not related in the cell lines used. Cell behavior differed using native HA, which induced PIP3 production, Akt phosphorylation and NFkB 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 NFkB activation, through a mechanism that differs from the one mediated by native HA.