1. [Rabdocoetsin B, a diterpenoid isolated from Isodon coetsa, is a potential proteasome inhibitor and induced apoptosis of t(8;21) leukemia cells].
- Author
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Feng T, Pu J, Hu Z, Liu D, Sun H, and Zhou G
- Subjects
- Antineoplastic Agents, Phytogenic pharmacology, Caspase 3 metabolism, Cell Line, Tumor, Diterpenes isolation & purification, Humans, Translocation, Genetic, Ubiquitins metabolism, Apoptosis drug effects, Diterpenes pharmacology, Isodon chemistry, Leukemia, Myeloid, Acute pathology, Proteasome Inhibitors
- Abstract
Effects of Rabdocoetsin B (Rabd-B), a diterpenoid extracted from Isodon coetsa, on t(8;21) leukemic cells was tested by CCK-8 assay and Flow cytometry. The A549 cells stably expressing pGC-E1-ZU1-GFP were treated with Rabd-B for 4 h, and the accumulation of GFP was detected by fluorescence microscope. Using Western blotting, we investigated the expression of Casp-3, PARP, S6', which is a subunit of the 19S regulatory complex of the 26S proteasome, and cellular ubiqutinated proteins. We found that Rabd-B induced growth inhibition and apoptosis of Kasumi-1 cells in a dose-dependent manner. In Kasumi-1 cells treated with 2.5 micromol/L Rabd-B for 24 h, pro-caspase-3 was processed into its active form. The substrate of Casp-3, poly ADP-ribose polymerase (PARP), was cleaved with generation of an 85 kD fragment. The increased GFP fluorescence intensity, cleavage of S6' and the accumulation of ubiquitinated proteins were found in Kasumi-1 cells treated with Rabd-B. These results suggested that Rabd-B is a potential proteasome inhibitor which induces programmed cell death of t(8;21) cells. Further study might provide evidence for employing Rabd-B in treating human t(8;21) leukemia.
- Published
- 2009