Sensitization by docosahexaenoic acid (DHA) of breast cancer cells to anthracyclines through loss of glutathione peroxidase (GPx1) response

Autor: Karine Mahéo, Philippe Bougnoux, Sophie Vibet, Jacques Goré, Jean-Paul Steghens, Caroline Goupille
Přispěvatelé: Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours
Jazyk: angličtina
Rok vydání: 2008
Předmět:
GPX1
Antioxidant
Docosahexaenoic Acids
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Antineoplastic Agents
Breast Neoplasms
Mammary Neoplasms
Animal
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Pharmacology
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Physiology (medical)
Cell Line
Tumor
medicine
Animals
Humans
Anthracyclines
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Reactive oxygen species
Glutathione Peroxidase
Chemistry
Vitamin E
Glutathione peroxidase
Glutathione
3. Good health
Rats
Gene Expression Regulation
Neoplastic
Oxidative Stress
Docosahexaenoic acid
030220 oncology & carcinogenesis
Female
lipids (amino acids
peptides
and proteins)
Reactive Oxygen Species
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Oxidative stress
Zdroj: Free Radical Biology and Medicine
Free Radical Biology and Medicine, Elsevier, 2008, 44 (7), pp.1483-1491. ⟨10.1016/j.freeradbiomed.2008.01.009⟩
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2008.01.009⟩
Popis: International audience; Docosahexaenoic acid (DHA, a lipid of marine origin) has been found to enhance the activity of several anticancer drugs through an oxidative mechanism. To examine the relation between chemosensitization by DHA and tumor cells antioxidant status, we used two breast cancer cell lines: MDA-MB-231, in which DHA increases sensitivity to doxorubicin, and MCF-7, which does not respond to DHA. Under these conditions, reactive oxygen species (ROS) level increased on anthracycline treatment only in MDA-MB-231. This was concomitant with a decreased cytosolic glutathione peroxidase (GPx1) activity, a crucial enzyme for protection against hydrogen and lipid peroxides, while major antioxidant enzyme activities increased in both cell lines in response to ROS. GPx-decreased activity was accompanied by an accumulation of glutathione, the GPx cosubstrate, and resulted from a decreased amount of GPx protein. In rat mammary tumors, when a DHA dietary supplementation led to an increased tumor sensitivity to anthracyclines, GPx1 activity was similarly decreased. Furthermore, vitamin E abolished both DHA effects on chemotherapy efficacy enhancement and on GPx1 inhibition. Thus, loss of GPx response to an oxidative stress in transformed cells may account for the ability of peroxidizable targets such as DHA to enhance tumor sensitivity to ROS-generating anticancer drugs.
Databáze: OpenAIRE
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