G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound

Maia Cabrera, Natalia Gomez, Federico Remes Lenicov, Emiliana Echeverría, Carina Shayo, Albertina Moglioni, Natalia Fernández, Carlos Davio, Ming Hsien Chien

研究成果: 雜誌貢獻文章

18 引文 斯高帕斯(Scopus)

摘要

Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4′-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies.

原文英語
文章編號0136878
期刊PLoS One
10
發行號9
DOIs
出版狀態已發佈 - 九月 11 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Cabrera, M., Gomez, N., Lenicov, F. R., Echeverría, E., Shayo, C., Moglioni, A., Fernández, N., Davio, C., & Chien, M. H. (2015). G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound. PLoS One, 10(9), [0136878]. https://doi.org/10.1371/journal.pone.0136878