glaucocalyxin-a and Leukemia

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.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Biomarkers; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Survival; Diterpenes, Kaurane; DNA Fragmentation; Drugs, Chinese Herbal; G1 Phase; HL-60 Cells; Humans; Inhibitory Concentration 50; Leukemia; Membrane Potential, Mitochondrial; Mitochondria; Reactive Oxygen Species; Signal Transduction