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Induction of Apoptosis by Gamisamgibopae-tang in A549 Human Lung Cancer Cells through Modulation of Bcl-2 Family and Activation of Caspases  

Kim, Hyun-Joong (Department of Oriental Medicine, Graduate School Dong-Eui University)
Kim, Hong-Gi (Department of Oriental Medicine, Graduate School Dong-Eui University)
Kim, Jin-Young (Department of Oriental Medicine, Graduate School Dong-Eui University)
Kam, Cheol-Woo (Department of Oriental Medicine, Graduate School Dong-Eui University)
Park, Dong-Il (Department of Oriental Medicine, Graduate School Dong-Eui University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.22, no.3, 2008 , pp. 630-641 More about this Journal
Abstract
Gamisamgibopae-tang (GMSGBPT) is a traditional Korean medicine, which has been used for patients suffering from a lung disease in Oriental medicine. In the present study, we examined the biochemical mechanisms of apoptosis by GMSGBPT in NCI-H460 and A549 human non-small-cell lung cancer cell lines. It was found that GMSGBPT could inhibit the cell proliferation of A549 cells in a concentration-dependent manner, however GMSGBPT did not affect the cell proliferation of NCI-H460 cells. Apoptotic cell death in A549 cells were detected using DAPI staining and annexin V fluorescein methods. The induction of apoptotic cell death by GMSGBPT was connected with a down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression, and proteolytic activation of caspase-3 and caspase-9 in A549 cells. However, GMSGBPT did not affect the levels of pro-apoptotic Bax and Bad expression, and activity of caspase-8. GMSGBPT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, phospholipase C-1 (PLC${\gamma}$1) and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings suggest that GMSGBPT may be a potential chemotherapeutic agent for the control of human non-small-cell lung cancer cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of GMSGBPT.
Keywords
Gamisamgibopae-tang; human non-small-cell lung cancer cells; apoptosis; caspase; Bcl-2;
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