151 Docosahexaenoic and Eicosahexaenoic N-3 Fatty Acids Inhibit DNA Synthesis and Cell Proliferation in Colorectal Cancer Cells Independent of the Responsible Underlying Molecular Pathways
| Autor: | Jessica Fernandez-Morales, Vanessa R. Sapoznik, Rosa M. Xicola, Anna Giros, Xavier Llor |
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| Rok vydání: | 2008 |
| Předmět: |
Programmed cell death
Hepatology Cell growth Chemistry Colorectal cancer Cell Gastroenterology Cell cycle medicine.disease Intestinal epithelium Cell biology chemistry.chemical_compound medicine.anatomical_structure Apoptosis medicine Cancer research lipids (amino acids peptides and proteins) Propidium iodide |
| Zdroj: | Gastroenterology. 134:A-27 |
| ISSN: | 0016-5085 |
| Popis: | Introduction: The intestinal epithelium undergoes a constant and fast renewal that is maintained in check thanks to a tight equilibrium between cell death and proliferation. An alteration of this equilibrium in the colonic epithelium can result in colorectal cancer development. Nutrients capable of either inducing programmed cell death or decreasing the proliferative rate of this epithelium could presumably be useful as either chemo preventive or even adjuvant therapeutic elements in colorectal cancer. Fish oil, through its main fatty acids, Docosahexaenoic (DHA) and Eicosahexaenoic (EPA) has shown some promising effects in colorectal cancer both, epidemiologically and experimentally. We have previously shown that DHA and EPA induce apoptosis in colorectal cancer cells. We also showed that both, the intrinsic and extrinsic pathways are involved though the down-regulation of two key elements: FLIP and XIAP. Aims: The aims of this study were: to determine if the n-3 fatty acids DHA and EPA can regulate colorectal cancer cell proliferation; to determine if this regulation is dependent on the type of molecular alterations present in these cells and; to determine if any phase of the cell cycle is affected in this potentially anti neoplastic effect. Methods: Non-confluent HCT116, LoVo, SW480, Caco-2 and HT-29 human colorectal cancer cells were grown in their regular media and, 24 h before the experiments, they were synchronized by feeding them with sera-free media supplemented with DHA, EPA or vehicle at final concentrations of 30 to 50 uM according to the type of cell studied. Cell proliferation was assessed by MTT analysis at 24 and 48h after fatty acid supplementation. Cell cycle phases were analyzed by flow citometry through propidium iodide staining. Results: DHA and EPA supplementation resulted in a decrease in the proliferation rate of most colorectal cancer cells, independently of APC, p53 or mismatch repair status. This coincided with a significant decrease in the DNA synthesis of these cells. Neither DHA nor EPA was able to stop proliferation of the metastatic LoVo cells. DNA synthesis was preserved in the latter cells as opposed to the non-metastatic cells. Conclusions: DHA and EPA can exert an anti neoplastic effect in colorectal cancer not only through a significant apoptosis induction but also through a significant decrease in cell proliferation and in DNA synthesis. These effects are independent of the responsible underlying molecular pathways. Metastatic colorectal cancer cells may have developed mechanisms that make these cells resistant to the anti proliferative effects of DHA and EPA. |
| Databáze: | OpenAIRE |
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