CDK1-cyclin B1 mediates the inhibition of proliferation induced by omega-3 fatty acids in MDA-MB-231 breast cancer cells.
Long-chain omega-3 polyunsaturated fatty acids are thought to inhibit the development of breast cancer. We investigated the effects of docosahexaenoic and eicosapentaenoic acids on the proliferation of MDA-MB-231 human mammary epithelial cells. Both docosahexaenoic and eicosapentaenoic acids decreased cell growth with a higher efficiency for docosahexaenoic acid (87% at 100 microM versus 74% for eicosapentaenoic acid). The effect on specific cell cycle phases was studied. G2/M duration was markedly increased by docosahexaenoic and by eicosapentaenoic acids (respectively by more than seven- and six-fold at 50 microM) when cells were synchronized at the G1/S boundary and released in the cell cycle. In contrast, there was no alteration of G1 or S phases. The expression of cyclin A, cyclin B1 and cyclin-dependent kinase 1, the regulators required for the progression from G2 to mitosis, were all decreased by these fatty acids (western blot). Since omega-3 fatty acids had no effect on the S phase, thus ruling out an involvement of cyclin A in their anti-proliferative effect, we examined whether the regulation of the cyclin-dependent kinase 1-cyclin B1 complex was altered. Upon omega-3 fatty acids treatment, cyclin B1 phosphorylation was inhibited and the expression of the cell division cycle 25C phosphatase, which dephosphorylates cyclin-dependent kinase 1, was decreased. We conclude that the anti-proliferative effect of omega-3 fatty acids occurs via the regulation of the cyclin-dependent kinase 1-cyclin B1 complex.
Barascu
Aurélia
A
Inserm, E 0211, Tours, F-37000, France; Université François-Rabelais de Tours, Tours, F-37000, France.
Besson
Pierre
P
Le Floch
Olivier
O
Bougnoux
Philippe
P
Jourdan
Marie-Lise
ML
D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010743:Phospholipids / Q000737:chemistry
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D015525:Fatty Acids, Omega-3; D010743:Phospholipids; D016203:CDC2 Protein Kinase