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| Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid isolated from Rabdosia japonicavar glaucocalyx, a traditional Chinese medicinal herb, which has been shown to inhibit tumor cell proliferation. Our results showed that GLA is a powerful growth inhibitor of K562, PC3, MCF-7 and KB cancer cells, IC50 ranged from 3～8.4 μM. Cell flow cytometry of GLA-treated KB cells showed a marked accumulation of cells in the S-phase and G2-phase fraction in a dose-dependent manner. In addition, staining for annexin V/PI, changes in nuclear morphology, and activation of caspase-9 and -3 support a role for apoptosis. Further investigation with squamous cell carcinoma KB cells found that GLA could induce an early lysosomal rupture within 6h as assessed by acridine-orange uptake. Additional experiments revealed that GLA could induce a dose-dependent accumulation of reactive oxygen species (ROS), trigger mitochondrial membrane permeabilization, release cytochrome c, and then down-regulate Bcl-2, up-regulate Bax. These results revealed that the cytoxicity of GLA was involved in a lysosomal-mitochondrial death pathwan |
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| Keywords:Glaucocalyxin A; reactive oxygen species;lysosome; mitochondria;apoptosis |
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