ABSTRACT
Objective: Colorectal cancer [CRC] is the second leading cause of cancer death in occidental countries. Chronic inflammatory bowel disease [crohn's disease and ulcerative colitis] is associated with an increased risk for CRC development. The aim of this work was to investigate the relationship between inflammatory status and absorption of nutrients with a role in CRC pathogenesis
Materials and Methods: In this experimental study, we evaluated the in vitro effect of tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IF-gamma], and acetylsalicylic acid on 14C-butyrate [14C-BT], 3H-folic acid [3H-FA] uptake, and on proliferation, viability and differentiation of Caco-2 and IEC-6 cells in culture
Results: The proinflammatory cytokines TNF-alpha and INF-gamma were found to decrease uptake of a low concentration of 14C-BT [10 micro M] by Caco-2 [tumoral] and IEC-6 [normal] intestinal epithelial cell lines. However, the effect of TNF-alpha and INF-gamma in IEC-6 cells is most probably related to a cytotoxic and antiproliferative impact. In contrast, INF-gamma increases uptake of a high concentration [10 mM] of 14C-BT in Caco-2 cells. The anticarcinogenic effect of BT [10 mM] in these cells is not affected by the presence of this cytokine. On the other hand, acetylsalicylic acid stimulates 14C-BT uptake by Caco-2 cells and potentiates its antiproliferative effect. Finally, both TNF-alpha and INF-gamma cause a significant decrease in 3H-FA uptake by Caco-2 cells
Conclusion: The inflammatory status has an impact upon cellular uptake of BT and FA, two nutrients with a role in CRC pathogenesis. Moreover, the anti-inflammatory acetylsalicylic acid potentiates the anticarcinogenic effect of BT in Caco-2 cells by increasing its cellular uptake