Storniolo Carolina E, Cabral Marisol, Busquets Maria A, Martín-Venegas Raquel, Moreno Juan J
Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona, Barcelona, Spain.
Front Pharmacol. 2020 Sep 4;11:529976. doi: 10.3389/fphar.2020.529976. eCollection 2020.
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 E 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.
结直肠癌（CRC）的病因至少部分与营养状况相关，流行病学数据表明膳食脂肪在CRC发病机制中起关键作用。此外，由花生四烯酸产生的炎症和类二十烷酸可能在CRC发展中起关键作用。然而，目前尚未完全研究特定脂肪酸（FAs）对肠道上皮细胞生长的影响。因此，本研究的目的是揭示不同饱和和不饱和长链脂肪酸（LCFA）以及一些LCFA代谢产物对CRC细胞系生长的影响及其可能的作用机制。我们的结果表明，油酸至少部分通过脂氧合酶途径合成的10-羟基-8-十八碳烯酸，是Caco-2细胞的一种有效的促有丝分裂因子，而多不饱和脂肪酸如二十碳五烯酸（EPA）根据其浓度具有双重行为效应。在高浓度下，EPA通过内在途径诱导细胞凋亡，而在低浓度下诱导细胞增殖，这可能与前列腺素E和12-羟基二十碳五烯酸等类二十烷酸的合成以及随后有丝分裂细胞信号通路（ERK 1/2、CREB、p38α）的诱导有关。因此，本研究有助于理解脂肪摄入与CRC之间的复杂关系。
