S-Adenosylmethionine-mediated apoptosis is potentiated by autophagy inhibition induced by chloroquine in human breast cancer cells

Journal of Cellular Physiology
Donatella Delle CaveMarina Porcelli

Abstract

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 low doses, raised the percentage of cells in G2 /M phase of cell cycle by down-regulating the expression of cell cycle-regulatory proteins cyclin B and cyclin E with a remarkable increase of p53, p27, and p21. We also 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 ...Continue Reading

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Citations

Feb 12, 2020·International Journal of Molecular Sciences·Patrycja Bronowicka-AdamskaMaria Wróbel
Oct 7, 2020·International Journal of Molecular Sciences·Annalisa PecoraroAnnapina Russo
Oct 21, 2020·Biomolecules & Therapeutics·Dong Wook Shin
Jan 15, 2021·Chemical Communications : Chem Comm·Shan WangKang-Kang Yu
Dec 8, 2020·Chemico-biological Interactions·Iza Mirela Rodini Garcia-PrincivalTeresinha Gonçalves da Silva
Dec 31, 2020·International Journal of Molecular Sciences·Laura MoscaAnnapina Russo

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