Differential sensitization of cancer cells to doxorubicin by DHA: A role for lipoperoxidation
| Autor: | Magali Lehman, Philippe Bougnoux, Jean Paul Steghens, Karine Mahéo, Sophie Vibet, Jacques Goré, Caroline Dartigeas |
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| Přispěvatelé: | Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Bougnoux, Philippe |
| Rok vydání: | 2005 |
| Předmět: |
Time Factors
Pharmacology medicine.disease_cause Biochemistry MESH: Lipid Peroxidation MESH: Drug Synergism Lipid peroxidation chemistry.chemical_compound 0302 clinical medicine MESH: Fatty Acids Omega-3 Malondialdehyde Neoplasms Vitamin E MESH: Neoplasms Phospholipids MESH: Glutathione chemistry.chemical_classification 0303 health sciences Antibiotics Antineoplastic Glutathione Disulfide Fatty Acids Drug Synergism Glutathione MESH: Fatty Acids 3. Good health MESH: Docosahexaenoic Acids Chemotherapy Adjuvant MESH: Chemotherapy Adjuvant Docosahexaenoic acid 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Oxidation-Reduction Polyunsaturated fatty acid medicine.drug MESH: Cell Line Tumor Docosahexaenoic Acids Anthracycline MESH: Malondialdehyde MESH: Oxida [SDV.CAN]Life Sciences [q-bio]/Cancer Biology MESH: Doxorubicin 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer Cell Line Tumor Physiology (medical) Fatty Acids Omega-3 medicine Humans Doxorubicin MESH: Antibiotics Antineoplastic 030304 developmental biology MESH: Humans Oxygen MESH: Glutathione Disulfide chemistry Lipid Peroxidation Oxidative stress |
| Zdroj: | Free Radical Biology and Medicine Free Radical Biology and Medicine, 2005, 39, pp.742-51. ⟨10.1016/j.freeradbiomed.2005.04.023⟩ Free Radical Biology and Medicine, Elsevier, 2005, 39, pp.742-51. ⟨10.1016/j.freeradbiomed.2005.04.023⟩ |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2005.04.023 |
| Popis: | Polyunsaturated fatty acids have been reported to enhance the cytotoxic activity of several anticancer drugs. In the present study, we observed that doxorubicin chemosensitization of breast cancer cell lines by docosahexaenoic acid (DHA, a long-chain omega-3 polyunsaturated fatty acid) was cell-line selective, affecting MDA-MB-231 and MCF-7 dox (a doxorubicin-resistant cell line) but not the parental MCF-7 cell line. DHA supplementation led to an increase in membrane phospholipid DHA level, but did not induce changes in intracellular [(14)C]doxorubicin accumulation. In MDA-MB-231, doxorubicin efficacy enhancement by DHA was linked to an increase in malondialdehyde level, a final product of lipid peroxidation. DHA elicited by itself a 3.7-fold malondialdehyde level increase, additive to that induced by doxorubicin. Addition of doxorubicin to DHA further increased the glutathione level, indicative of the generation of an oxidative stress. In contrast to MDA-MB-231, doxorubicin did not increase the malondialdehyde level in MCF-7, although DHA induced lipid peroxidation. Therefore in MCF-7, lipid peroxidation induced by DHA itself was not sufficient to trigger an oxidative stress and to subsequently increase sensitivity to doxorubicin. These data indicate that the differential effect of DHA among cells on drug toxicity results from a differential oxidative response to doxorubicin. Chemosensitization through fatty acids appears as a new promising adjuvant therapeutic paradigm, since omega-3 fatty acids are physiological molecules found in food and are nontoxic in vivo. |
| Databáze: | OpenAIRE |
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