Rabdocoetsin B, a diterpenoid isolated from Isodon coetsa, is a potential proteasome inhibitor and induced apoptosis of t(8;21) leukemia cells.
- Author:
Tingting FENG
1
;
Jianxin PU
;
Zheng HU
;
Dapeng LIU
;
Handong SUN
;
Guangbiao ZHOU
Author Information
1. Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents, Phytogenic;
pharmacology;
Apoptosis;
drug effects;
Caspase 3;
metabolism;
Cell Line, Tumor;
Diterpenes;
isolation & purification;
pharmacology;
Humans;
Isodon;
chemistry;
Leukemia, Myeloid, Acute;
pathology;
Proteasome Inhibitors;
Translocation, Genetic;
Ubiquitins;
metabolism
- From:
Chinese Journal of Biotechnology
2009;25(8):1218-1224
- CountryChina
- Language:Chinese
-
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.
