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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number0136878
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 11 2015

Fingerprint

G2 Phase Cell Cycle Checkpoints
Thiosemicarbazones
benzophenone
leukemia
Tumors
Leukemia
Apoptosis Regulatory Proteins
apoptosis
Cells
Apoptosis
neoplasms
Chemical activation
cell lines
Cell Line
Neoplasms
Phosphorylation
Mitochondria
MAP Kinase Signaling System
Mitochondrial Membrane Potential
Cell death

ASJC Scopus subject areas

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

Cite this

G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound. / Cabrera, Maia; Gomez, Natalia; Lenicov, Federico Remes; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos; Chien, Ming Hsien.

In: PLoS One, Vol. 10, No. 9, 0136878, 11.09.2015.

Research output: Contribution to journalArticle

Cabrera, M, Gomez, N, Lenicov, FR, Echeverría, E, Shayo, C, Moglioni, A, Fernández, N, Davio, C & Chien, MH 2015, 'G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound', PLoS One, vol. 10, no. 9, 0136878. https://doi.org/10.1371/journal.pone.0136878
Cabrera, Maia ; Gomez, Natalia ; Lenicov, Federico Remes ; Echeverría, Emiliana ; Shayo, Carina ; Moglioni, Albertina ; Fernández, Natalia ; Davio, Carlos ; Chien, Ming Hsien. / G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound. In: PLoS One. 2015 ; Vol. 10, No. 9.
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