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Gardenin B-induced Cell Death in Human Leukemia Cells Involves Multiple Caspases but Is Independent of the Generation of Reactive Oxygen Species

Gardenin B-induced Cell Death in Human Leukemia Cells Involves Multiple Caspases but Is Independent of the Generation of Reactive Oxygen Species

Javier Cabrera, Ester Saavedra, Henoc Del Rosario, Juan Perdomo, Juan F Loro, Diego A Cifuente, Carlos E Tonn, Celina García, José Quintana, Francisco Estévez

Chem Biol Interact. 2016 Aug 25;256:220-7.

PMID: 27423764

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2798201	Gardenin B		2798-20-1	Price

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