Carcinogenesis, Vol. 23, No. 5, 735-740,
May 2002
© 2002 Oxford University Press
CANCER BIOLOGY |
Modulation of angiogenesis-related proteins synthesis by sodium butyrate in colon cancer cell line HT29
Department of Experimental Oncology, Determinants of Prognosis and Treatment Response Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy
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)-1
, 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-1 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-1 protein level, whereas after a longer time of exposure HIF-1 level increased in the presence of a high NaB concentration (2 mM) with a concomitant increase in HIF-1 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.
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