Induction of G2/M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells

Fabio Nicolini, Olga Burmistrova, María Teresa Marrero, Fernando Torres, Cristina Hernández, José Quintana, Francisco Estévez

Research output: Contribution to journalArticlepeer-review

Abstract

Flavonoids are naturally occurring polyphenolic compounds which display a vast array of biological activities. In this study, we investigated the effects of tamarixetin on viability of human tumor cell lines and found that it was cytotoxic against leukemia cells and in particular P-glycoprotein-overexpressing K562/ADR cells. This compound inhibited proliferation in a concentration- and time-dependent manner, induced apoptosis and blocked cell cycle progression at G2-M phase. This was associated with the accumulation of cyclin B1, Bub1 and p21Cip1/Waf-1, changes in the phosphorylation status of cyclin B1, Cdk1, Cdc25C and MPM-2, and inhibition of tubulin polymerization. Moreover, cell death was found to be associated with cytochrome c release and cleavage of caspases and of poly(ADP-ribose) polymerase, and completely abrogated by the free-radical scavenger N-acetyl-L-cysteine. The sensitivity of leukemic cells to tamarixetin suggests that it should be considered for further preclinical and in vivo testing.

Original languageEnglish
Pages (from-to)939-950
Number of pages12
JournalMolecular Carcinogenesis
Volume53
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Flavonoids

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Medicine(all)

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