13-Hydroxy-15-oxo-zoapatlin, an ent-kaurane diterpene, induces apoptosis in human leukemia cells, affecting thiol-mediated redox regulation

Fabrizio Dal Piaz, Patrizia Nigro, Alessandra Braca, Nunziatina De Tommasi, Maria Antonietta Belisario

Research output: Contribution to journalArticlepeer-review

Abstract

13-Hydroxy-15-oxo-zoapatlin (OZ), a nor-kaurane diterpene, was first described as a compound inhibiting the proliferation of human cancer cell lines. Successively, it was reported that OZ inhibits the G2 DNA damage checkpoint and causes mitotic arrest. To get more insight into the molecular mechanism(s) underlying the antitumor potential of OZ, we evaluated the proapoptotic activity of this molecule. OZ was found to induce hypodiploidia and phosphatidylserine externalization, two hallmarks of apoptosis; to disrupt mitochondrial membrane potential; and to trigger caspase-3 activation. OZ-induced cell death, mostly dependent upon the presence of the α,β-carbonyl group, is strongly related to alterations in the cellular redox balance. The interaction of OZ with cellular components and proteins containing reactive thiols was evaluated by mass spectrometry-based approaches. A specific reactivity of this compound toward glutathione and thioredoxin was observed.

Original languageEnglish
Pages (from-to)1409-1422
Number of pages14
JournalFree Radical Biology and Medicine
Volume43
Issue number10
DOIs
Publication statusPublished - Nov 15 2007

Keywords

  • Apoptosis
  • Cellular redox balance
  • Diterpene
  • Free radicals
  • Glutathione
  • Thioredoxin

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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