TY - JOUR
T1 - 13-Hydroxy-15-oxo-zoapatlin, an ent-kaurane diterpene, induces apoptosis in human leukemia cells, affecting thiol-mediated redox regulation
AU - Dal Piaz, Fabrizio
AU - Nigro, Patrizia
AU - Braca, Alessandra
AU - De Tommasi, Nunziatina
AU - Belisario, Maria Antonietta
PY - 2007/11/15
Y1 - 2007/11/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cellular redox balance
KW - Diterpene
KW - Free radicals
KW - Glutathione
KW - Thioredoxin
UR - http://www.scopus.com/inward/record.url?scp=34948888792&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948888792&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2007.07.022
DO - 10.1016/j.freeradbiomed.2007.07.022
M3 - Article
C2 - 17936187
AN - SCOPUS:34948888792
VL - 43
SP - 1409
EP - 1422
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 10
ER -