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Title: Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species
Authors: Cabrera, J.
Saavedra Díaz, Ester Gloria 
del Rosario, Henoc
Perdomo, Juan 
Loro, Juan F. 
Cifuente, Diego A.
Tonn, Carlos E.
García, Celina
Quintana, Jose 
Estévez, Francisco 
UNESCO Clasification: 2403 Bioquímica
Keywords: Apoptosis
Baccharis scandens
Issue Date: 2016
Journal: Chemico-biological interactions (Print) 
Abstract: Flavonoids have attracted great interest due to their possible anticancer activities. Here we investigated the antiproliferative activity of the flavonoids isolated from Baccharis scandens against human leukemia cell lines and found that the methoxyflavonoid gardenin B was the most cytotoxic compound against HL-60 and U-937 cells, showing IC50 values between 1.6 and 3.0 μM, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. These effects on viability were accompanied by the concentration- and time-dependent appearance of apoptosis as evidenced by DNA fragmentation, formation of apoptotic bodies and a sub-G1 ratio increase. Comparative studies with the best-studied bioflavonoid quercetin indicate that gardenin B is a more cytotoxic and more apoptotic inducer than quercetin. Cell death induced by gardenin B was associated with: (i) a significant induction of caspase-2, -3, -8 and -9 activities; (ii) cleavage of the initiator caspases (caspase-2, -8 and -9), of the executioner caspase-3, and of poly(ADP-ribose) polymerase; and (iii) a concentration-dependent reactive oxygen species generation. In conclusion, apoptosis induced by gardenin B is associated with activation of both the extrinsic and the intrinsic apoptotic pathways of cell death and occurs through a mechanism that is independent of the generation of reactive oxygen species.
ISSN: 0009-2797
DOI: 10.1016/j.cbi.2016.07.016
Source: Chemico-Biological Interactions[ISSN 0009-2797],v. 256, p. 220-227
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