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Toxicol In Vitro. 2011 Feb;25(1):51-63. doi: 10.1016/j.tiv.2010.09.006. Epub 2010 Sep 17.

Glaucocalyxin A induces apoptosis in human leukemia HL-60 cells through mitochondria-mediated death pathway.

Author information

1
School of Pharmaceutical Sciences, Soochow University, Suzhou, PR China.

Abstract

Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid isolated from Rabdosia japonica var. glaucocalyx, a traditional Chinese medicinal herb, which has been shown to inhibit tumor cell proliferation. However, the mechanism underlying GLA-induced cytotoxicity remains unclear. In this study, we focused on the effect of GLA induction on apoptosis, the mitochondria-mediated death pathway and the accumulation of reactive oxygen species (ROS) in human leukemia cells (HL-60). GLA could induce a dose-dependent apoptosis in HL-60 cells as characterized by cell morphology, DNA fragmentation, activation of caspase-3, -9 and an increased expression ratio of Bax/Bcl-2. The mitochondrial membrane potential (Δψ(m)) loss and cytochrome c release from mitochondria to cytosol were observed during the induction. Moreover, GLA caused a time- and dose-dependent elevation of intracellular ROS level in HL-60 cells, and N-acetyl-l-cysteine (NAC, a well-known antioxidant) could block GLA-induced ROS generation and apoptosis. These data suggest that GLA induces apoptosis in HL-60 cells through ROS-dependent mitochondrial dysfunction pathway.

PMID:
20851175
DOI:
10.1016/j.tiv.2010.09.006
[Indexed for MEDLINE]

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