Open AccessInduction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells
Author(s) -
Cheol Park,
Yang-Ho Choi,
Sook Kyung Hyun,
Hyun Ju Kwon,
Hye Jin Hwang,
GiYoung Kim,
Byung Tae Choi,
Byung-Woo Kim,
IlWhan Choi,
SungKwon Moon,
Wun-Jae Kim,
Yung Hyun Choi
Publication year - 2009
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm_00000258
Subject(s) - cyclin dependent kinase , cell cycle , apoptosis , schisandra chinensis , cdk inhibitor , cyclin d1 , u937 cell , chemistry , cell cycle checkpoint , poly adp ribose polymerase , biology , biochemistry , medicine , enzyme , polymerase , alternative medicine , traditional chinese medicine , pathology
We isolated two phytochemical lignans, schisandrin and schisandrin C, from Schizandra chinensis Baill and investigated their anti-cancer effects in human leukemia U937 cells. Schisandrin C inhibited cell growth in a dose-dependent manner, which was associated with the induction of G1 arrest of the cell cycle and apoptosis; schisandrin did not inhibit growth. Schisandrin C induced G1 arrest was correlated with down-regulation of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk) 4 and E2Fs expression, inhibition of phosphorylation of retinoblastoma protein (pRB), and up-regulation of the Cdk inhibitor p21(WAF1/CIP1). In addition, schisandrin C-induced apoptosis was associated with down-regulation of expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, proteolytic activation of caspase-3 and -9, and a concomitant degradation of poly(ADP-ribose) polymerase (PARP). Furthermore, schisandrin C-induced apoptosis was significantly inhibited by a caspase-3 specific inhibitor z-DEVD-fmk, indicating an important role for caspase-3 in the schisandrin C mechanism. In summary, growth inhibition by schisandrin C is related to cell cycle arrest at G1 and induction of caspase-3-dependent apoptosis in U937 cells; these findings suggest that schisandrin C may be a useful chemotherapeutic agent.