Abstract
Etiology of colorectal cancer (CRC) is related, at least in part, with nutritional profile and epidemiological data indicating a key role of dietary fat on CRC pathogenesis. Moreover, inflammation and eicosanoids produced from arachidonic acid might have a pivotal role in CRC development. However, the effect of specific fatty acids (FAs) on intestinal epithelial cell growth is not completely studied now. By this reason, the aim of this work is to unravel the effect of different saturated and unsaturated long-chain fatty acids (LCFA) and some LCFA metabolites on CRC cell line growth and their possible mechanisms of action. Our results demonstrated that oleic acid is a potent mitogenic factor to Caco-2 cells, at least in part, through 10-hydroxy-8-octadecenoic synthesized by lipoxigenase pathway, whereas polyunsaturated FAs such as eicosapentaenoic (EPA) acid has a dual behavior effect depending on its concentration. A high concentration, EPA induced apoptosis through intrinsic pathway, whereas at low concentration induced cell proliferation that could be related to the synthesis of eicosanoids such as prostaglandin E3 and 12-hydroxyeicosapentaenoic acid and the subsequent induction of mitogenic cell signaling pathways (ERK 1/2, CREB, p38α). Thus, this study contributes to understand the complicated relationship between fat ingest and CRC.
Highlights
Cancer causes around 7 million of deaths annually, becoming 12.5% in the entire world and colorectal cancer (CRC) is the third leading cause of cancer-related death in developed countries (Ullman and Itzkowitz, 2011)
When undifferentiated Caco-2 cells were incubated with different long-chain fatty acids (LCFA) in absence of fetal bovine serum (FBS) we observed that palmitoleic (10–100 μM), oleic (1–100 μM), myristoleic (100 μM), and elaidic (100 μM) acids as well as the lowest EPA and DHA concentration (10 μM) induced cell proliferation (Figure 1A)
Saturated LCFAs did not have any effect on Caco-2 cell growth, oleic acid was the most mitogenic monounsaturated FAs (MUFAs) assayed; and EPA as a representative PUFA, presented a dual effect on Caco-2 cell growth depending on concentration and the presence of FBS
Summary
Cancer causes around 7 million of deaths annually, becoming 12.5% in the entire world and colorectal cancer (CRC) is the third leading cause of cancer-related death in developed countries (Ullman and Itzkowitz, 2011). The lifetime risk of developing CRC is 4.3% (NCI). CRC is linked with environmental factors, being lifestyle and nutritional profile the major but controllable implicated factors. Around 90% of the CRC cases appear to be related to lifestyle, with the highest incidence in economically developed countries (Clinton et al, 2020). Alcoholic beverages, red and processed meat, saturated fat, and a high energy intake, specially associated with abdominal body fatness, would favor CRC development. Westernized diet pattern is associated with an increased risk for CRC (Yusof et al, 2012)
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