التفاصيل البيبلوغرافية
| العنوان: |
S-Adenosylmethionine-mediated apoptosis is potentiated by autophagy inhibition induced by chloroquine in human breast cancer cells. |
| المؤلفون: |
Cave, Donatella Delle, Desiderio, Vincenzo, Mosca, Laura, Ilisso, Concetta P., Mele, Luigi, Caraglia, Michele, Cacciapuoti, Giovanna, Porcelli, Marina |
| المصدر: |
Journal of Cellular Physiology; Feb2018, Vol. 233 Issue 2, p1370-1383, 14p |
| مصطلحات موضوعية: |
APOPTOSIS, ADENOSYLMETHIONINE, AUTOPHAGY, CHLOROQUINE, BREAST cancer, CANCER cells, DISEASE risk factors, THERAPEUTICS |
| مستخلص: |
The naturally occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis. AdoMet consistently enhanced the levels of the autophagy markers beclin-1 and LC3B-II, and caused a significant increase of pro-apoptotic Bax/Bcl-2 ratio paralleled by poly (ADP ribose) polymerase (PARP) and caspase 9, and 6 cleavage. Notably, AdoMet, already at lowdoses, raised the percentage of cells in G2/M phase of cell cycle by down-regulating the expression of cell cycleregulatory proteins cyclinBandcyclin Ewith a remarkable increase of p53,p27, and p21. Wealso evaluated the combination of AdoMet and the autophagy inhibitor chloroquine (CLC) showing that autophagy block is synergistic in inducing both growth inhibition and apoptosis. These effects were paralleled by a strong inhibition of the activity of AKT and of the downstream effector mTOR and by an increased cleavageof caspase-6andPARP. These data suggest, for the first time, that autophagy can act as an escape mechanism from the apoptotic activity of AdoMet, and that AdoMet could be used in combination with CLC or its analogs in the treatment of breast cancer. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
