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KMID : 0363320110320040565
Journal of Korean Oriental Internal Medicine
2011 Volume.32 No. 4 p.565 ~ p.583
Anti-proliferative and Pro-apoptic Effects of Dan-Seon-Tang in Human Leukemia Cells
Kim Seong-Hwan

Park Sang-Eun
Hong Sang-Hoon
Abstract
Objectives: This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells.

Methods: U937 cells were exposed to DST and growth inhibition was measured by MTT assay.

Results: Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-¥ã1, ¥â-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3.

Conclusion: These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.
KEYWORD
human leukemia, apoptosis, Agrimonia pilosa Ledeb, Codonopsis pilosula(Fr.) Nannf, Salviae miltiorrhizae
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