N-3 PUFAs have antiproliferative and apoptotic effects on human colorectal cancer stem-like cells in vitro
Autor: | Sheng Zhang, Haixia Zhang, Honglan Yu, Yan Zhang, Conglong Xue, Yu-Fei Li, Zhanqiang Zhang, Ting Yang, Hanping Shi, Kaitao Yuan, Shi Fang, Lixiao Xu |
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Rok vydání: | 2013 |
Předmět: |
Docosahexaenoic Acids
genetic structures Mitomycin Endocrinology Diabetes and Metabolism Clinical Biochemistry Fluorescent Antibody Technique Mice Nude Antineoplastic Agents Apoptosis DNA Fragmentation Biology Biochemistry Mice Cancer stem cell Cell Line Tumor Spheroids Cellular medicine Animals Humans Annexin A5 Molecular Biology Cell Proliferation chemistry.chemical_classification Nutrition and Dietetics Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Cancer Cell cycle medicine.disease Eicosapentaenoic acid Eicosapentaenoic Acid Gene Expression Regulation chemistry Docosahexaenoic acid Neoplastic Stem Cells Cancer research Female lipids (amino acids peptides and proteins) Fluorouracil Colorectal Neoplasms Polyunsaturated fatty acid |
Zdroj: | The Journal of Nutritional Biochemistry. 24:744-753 |
ISSN: | 0955-2863 |
DOI: | 10.1016/j.jnutbio.2012.03.023 |
Popis: | The n-3 polyunsaturated fatty acids have been shown to inhibit the induction and progression of many kinds of tumor and to increase the therapeutic effects of numerous chemotherapeutics, but their anticancer effect on cancer stem cells from colorectal cancer has not been described previously. In the present study, we cultivated spheres from the SW620 cell line in serum-free medium and evaluated the features of the spheres by immunofluorescence, cell cycle distribution, resistance to chemotherapeutics and soft agar clone formation, and the spheres were shown to be cancer stem-like cells through tumorigenicity in athymic nude mice. Reverse transcriptase polymerase chain reaction analysis of pluripotency genes, such as Sox-2, Oct-4 and Bmi-1, showed that the spheres were generated by dedifferentiation of SW620 cells. The study explored the use of n-3 polyunsaturated fatty acids (PUFAs) in spheres, which were treated with two n-3 PUFAs [docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA)]. Treatment of the spheres with DHA and EPA alone or in combination for 72 h led to apoptosis and the progressive loss of viability and DNA fragmentation and an increase in annexin V expression. DHA and EPA can enhance the chemotherapeutic sensitivity effect of 5-Fu and mitomycin C, especially DHA combined with EPA. Taken together, these results provide evidence that n-3 PUFAs exert a direct anticancer action that may contribute to their antiproliferative and proapoptotic effect on the cancer stem-like cells. |
Databáze: | OpenAIRE |
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