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Inhibitory effects of epoxy metabolites of docosahexaenoic acid on human colon cancer stem cells (261.3)
Author(s) -
Xu Fei,
Lee Sing,
Hammock Bruce,
Zhang Guodong,
Xiao Hang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.261.3
Subject(s) - colorectal cancer , docosahexaenoic acid , cancer stem cell , inhibitory postsynaptic potential , stem cell , cancer research , cancer cell , cancer , cell culture , medicine , chemistry , pharmacology , biochemistry , fatty acid , biology , microbiology and biotechnology , polyunsaturated fatty acid , genetics
Epidemiological and preclinical evidence supports that omega‐3 dietary fatty acids such as DHA reduce the risks of cancers, but the underlying mechanisms are poorly understood. Epoxydocosapentaenoic acids (EDPs) are the cytochrome P450 epoxygenases (CYP450) metabolites of DHA, and have been reported to mediate some of the health‐promoting effects of DHA. Increasing evidence suggests that cancer stem cells (CSCs) may be responsible for occurrence of malignant tumors. Herein we investigated the inhibitory effect of EDPs on human colon CSCs. CSC‐ associated tumor spheres were obtained from human cancer stem cells. The inhibitory effect of 19, 20‐EDP and a mixture of six different EDPs (i.e. 7‐, 8‐, 10, 11‐, 13, 14‐, 16, 17‐ and 19, 20‐EDP) were determined on both HT29 and HCT116 colon cancer cells. The results showed that both 19, 20‐EDP and EDPs mix showed a dose‐dependent inhibition on human colon CSCs. For example, treatment with 19, 20‐EDP at 1µM for 10 days caused 55% inhibition on tumor spheres derived from HT29 cells, while EDPs mix at same total concentration caused 71% inhibition. Most interestingly, 19, 20‐EDP and EDPs mix at a very low concentration of 0.1 µM still resulted in significant inhibition (33% and 55%, respectively) on tumor spheres derived from HT29 cell line. Overall, our study for the first time demonstrated the inhibitory effects of EDPs on human colon CSCs. Grant Funding Source : Supported by funding from NIH, AICR and USDA