Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells.

Abstract:

: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.

journal_name

Int J Mol Med

authors

Park C,Choi YW,Hyun SK,Kwon HJ,Hwang HJ,Kim GY,Choi BT,Kim BW,Choi IW,Moon SK,Kim WJ,Choi YH

doi

10.3892/ijmm_00000258

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

495-502

issue

4

eissn

1107-3756

issn

1791-244X

journal_volume

24

pub_type

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