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Glaucocalyxin A induces apoptosis in human leukemia HL60 cells through mitochondria-mediated death pathway

Glaucocalyxin A induces apoptosis in human leukemia HL60 cells through mitochondria-mediated death pathway,10.1016/j.tiv.2010.09.006,Toxicology in Vit

Glaucocalyxin A induces apoptosis in human leukemia HL60 cells through mitochondria-mediated death pathway   (Citations: 1)
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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 (Δψm) 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.
Journal: Toxicology in Vitro - TOXICOL VITRO , vol. 25, no. 1, pp. 51-63, 2011
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    • ...Because the activation of intrinsic pathway is often related to the Bax/Bcl-2 expression or its ratio [22], the Bax and Bcl-2 expression were detected; the results indicated that the expression of Bax was upregulated, the expression of Bcl-2 was downregulated, and the ratio of Bax/Bcl-2 was upregulated, which was related to the activation of Caspase 9 and Caspase 3...

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