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

  • Authors:
    • Cheol Park
    • Young-Whan Choi
    • Sook Kyung Hyun
    • Hyun Ju Kwon
    • Hye Jin Hwang
    • Gi-Young Kim
    • Byung Tae Choi
    • Byung-Woo Kim
    • Il-Whan Choi
    • Sung-Kwon Moon
    • Wun-Jae Kim
    • Yung Hyun Choi
  • Corresponding author:
  • View Affiliations

  • Published online on: Thursday, October 1, 2009
  • Pages: 495-502
  • DOI: 10.3892/ijmm_00000258

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 Cover

October 2009
Volume 24 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

2013 Impact Factor: 1.88
Ranked #27/122 Medicine Research and Experimental
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APA
Park, C., Choi, Y., Hyun, S.K., Kwon, H.J., Hwang, H.J., Kim, G. ... Choi, Y.H. (2009). Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells. International Journal of Molecular Medicine, 24, 495-502. http://dx.doi.org/10.3892/ijmm_00000258
MLA
Park, C., Choi, Y., Hyun, S. K., Kwon, H. J., Hwang, H. J., Kim, G., Choi, B. T., Kim, B., Choi, I., Moon, S., Kim, W., Choi, Y. H."Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells". International Journal of Molecular Medicine 24.4 (2009): 495-502.
Chicago
Park, C., Choi, Y., Hyun, S. K., Kwon, H. J., Hwang, H. J., Kim, G., Choi, B. T., Kim, B., Choi, I., Moon, S., Kim, W., Choi, Y. H."Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells". International Journal of Molecular Medicine 24, no. 4 (2009): 495-502. http://dx.doi.org/10.3892/ijmm_00000258