Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells.
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.
Park
Cheol
C
Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan 614-052, Korea.
Choi
Young-Whan
YW
Hyun
Sook Kyung
SK
Kwon
Hyun Ju
HJ
Hwang
Hye Jin
HJ
Kim
Gi-Young
GY
Choi
Byung Tae
BT
Kim
Byung-Woo
BW
Choi
Il-Whan
IW
Moon
Sung-Kwon
SK
Kim
Wun-Jae
WJ
Choi
Yung Hyun
YH
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D034242:Cyclooctanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry*; D020298:U937 Cells
D000972:Antineoplastic Agents, Phytogenic; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; C031409:schizandrin C