Lack of Enhancing Effect of Lauric Acid on the Development of Aberrant Crypt Foci in Male ICR Mice Treated with Azoxymethane and Dextran Sodium Sulfate

Abstract

Abstract:The effect of lauric acid (LA), which is reported to induce cyclooxygenase (COX)-2 expression in macrophage cells (RAW 264.7) on the development of aberrant crypt foci (ACF), putative precursor lesions of colonic adenocarcinoma, was investigated in an inflammation-related mouse colon carcinogenesis model treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). To induce ACF, male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight) and then followed by 1% DSS in drinking water for one week, starting one week after dosing of AOM (AOM/DSS group). The AOM/DSS/LA group was fed with a diet containing 1% LA for 7 weeks, starting one week after the cessation of DSS administration. Other groups included the AOM/LA group given AOM and 1% LA diet for 9 weeks, the DSS/LA group given DSS and the diet with 1% LA, the AOM group that received AOM alone, the DSS group given DSS alone in drinking water, the LA group fed with 1% LA-containing diet alone, and the untreated group. At week 10 (end of the study), the frequency of ACF did not significantly differ between the AOM/DSS group (7.4 ± 3.0) and the AOM/DSS/LA group (8.4 ± 5.0). The value was extremely low in the AOM/LA group (1.0 ± 1.0) and in the AOM alone group (2.4 ± 2.7). No ACF developed in other groups. Our findings suggest that dietary LA did not influence the occurrence of ACF in the AOM/DSS-induced mouse colon tumorigenesis, indicating a lack of LA enhancing effects on the early phase of inflammation-related mouse colon carcinogenesis. (J Toxicol Pathol 2007; 20: 93-100)

Fatty acids as potential adjunctive colorectal chemotherapeutic agents

“…These longer chain length (saturated) forms of FA occur naturally in coconut and palm kernel oils and some milk fats. 74,75 MCFAs act as drug absorption enhancers via modification of tight gap proteins to increase delivery of drugs with low oral availability. 76,77 To this end, both capric and lauric acids decrease trans-epithelial resistance (R T ) in airway epithelium cells, altering claudin or tight gap junctions proteins via a Ca 2+ independent mechanism.…”

“…In the CRC context, in vivo administration of lauric acid to mice with azoxymethane-induced CRC did not show any increase in the formation of aberrant crypts. 74 Further studies into the potential anti-neoplastic properties of MCFA are therefore warranted.…”