Modulation of angiogenesis-related proteins synthesis by sodium butyrate in colon cancer cell line HT29.
Sodium butyrate (NaB), a short-chain fatty acid naturally present in the human colon, is able to induce cell cycle arrest, differentiation and apoptosis in colon cancer cells. In addition to these effects, we investigated the effect of NaB on two angiogenesis-related proteins in a colon carcinoma cell line (HT29): vascular endothelial growth factor (VEGF), the most potent angiogenic factor, and hypoxia-inducible factor (HIF)-1alpha, the main transcription activator of the VEGF gene, which are both constitutively expressed at high levels in HT29 also in normoxic conditions. NaB treatment had a different effect on VEGF165 and HIF-1alpha expression. In fact, it induced a dose-dependent down regulation of the VEGF165 protein level that was not paralleled by a concomitant down regulation of the corresponding mRNA, suggesting a post-translational regulation of the factor. Conversely, after 24 h of treatment all the tested NaB concentrations reduced the HIF-1alpha protein level, whereas after a longer time of exposure HIF-1alpha level increased in the presence of a high NaB concentration (2 mM) with a concomitant increase in HIF-1alpha mRNA. These results indicate that NaB, besides regulating other fundamental cellular processes, is able to modulate the expression of two important angiogenesis-related molecules and suggested a further possible clinical application of this short-chain fatty acid as an anti-angiogenic compound in association with conventional chemotherapeutic agents.
Pellizzaro
Cinzia
C
Department of Experimental Oncology, Determinants of Prognosis and Treatment Response Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Coradini
Danila
D
Daidone
Maria Grazia
MG
D020148:Butyric Acid / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020148:Butyric Acid