Title: Opposite Expression of Securin and gamma-H2AX Regulates Baicalein-Induced Cancer Cell Death
Authors: Jiang, Ren-Huei
Su, Wen-Chi
Liu, Huei-Fang
Huang, Hou-Syun
Chao, Jui-I
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
Issue Date: 1-Oct-2010
Abstract: Securin and gamma-H2AX have been shown to regulate cell survival and genomic stability. However, it is still unknown how the expression and regulation of these proteins is altered following treatment with baicalein, a natural flavonoid extracted from the Scutellaria baicalensis root. In the present study, we investigate the possible roles of securin and gamma-H2AX in baicalein-induced cancer cell death. Baicalein reduced cell viability in a variety of human cancer cell lines, including bladder, cervical, colon, and lung cancer cells. Interestingly, baicalein treatment (40-80 mu M for 24 h) markedly inhibited securin expression, while the levels of gamma-H2AX were elevated. Abnormal spindle formation and chromosomal segregation were induced by baicalein. Furthermore, wild type HCT116 cancer cells had a higher incidence of cytotoxicity and apoptosis than securin-null HCT116 cells following treatment with baicalein. In contrast, baicalein increased the levels of gamma-H2AX to a similar extent in both cell types. Transfection with H2AX siRNA further increased baicalein-induced cell death. Additionally, blockade of the AKT pathway by treatment with wortmannin or AKT shRNA lowered the levels of gamma-H2AX and enhanced cytotoxicity in baicalein-treated cells. Taken together, our findings suggest that the opposing effects of baicalein on securin and gamma-H2AX levels may be involved in the regulation of cell viability and genomic stability by this compound. J. Cell. Biochem. 111: 274-283, 2010. (C) 2010 Wiley-Liss, Inc.
URI: http://dx.doi.org/10.1002/jcb.22697
ISSN: 0730-2312
DOI: 10.1002/jcb.22697
Volume: 111
Issue: 2
Begin Page: 274
End Page: 283
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