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Journal of Biochemistry Advance Access published online on May 31, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn074
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© 2008 The Japanese Biochemical Society

Valproic Acid Inhibits the Growth of Cervical Cancer both In vitro and In vivo

Siraj Sami1, Naseruddin Höti2, Han-Mei Xu1,*, Zilong Shen1 and Xiaofeng Huang3

1. The Center of Biotechnology, College of Life Sciences and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
2. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Baltimore, MD 21287-2101, USA
3. Department of Oral Pathology, Nanjing Stomatological Hospital, Affiliated Medical School, Nanjing University, Nanjing 210093, People's Republic of China.

*Corresponding Author: Han-Mei Xu. The Center of Biotechnology, College of Life Sciences and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Tel.: +86 25 8327 1007 Fax: +86 25 85438355, E-mail: xuhanmei{at}yahoo.com.cn.

Received February 18, 2008; Accepted May 22, 2008


  Abstract

Summary

Valproic acid (VPA), a well known anticonvulsant, is currently under extensive evaluation as an anticancer agent. It is known to exert its anticancer effect mainly by inhibiting the enzyme Histone Deacetylase I. In our study, we investigated the effects of VPA on cervical cancer both in vitro and in vivo cancer models. We examined the effects of acute VPA (0, 1.2, 2.4, 5.0mM) treatment on cell proliferation in cervical cancer cell lines HeLa, SiHa and Ca Ski and Histone acetylation, p21 and p53 gene expression in HeLa cell line. We also investigated the effect of chronic VPA administration in tumor xenograft growth studies. Our results show that with acute treatment, VPA can increase the expression of net Histone H3 acetylation and up-regulate p21 expression with no effect on p53 expression. Chronic administration of VPA had a net cytostatic effect that resulted in a statistically significant reduction of tumor growth and improved survival advantages in tumor xenografts studies. Furthermore, we also demonstrated that VPA has a direct anti-angiogenic effect in tumor studies and could potentially be a promising candidate for further cervical cancer trails.

Key Words: Angiogenesis, Cervical Cancer, p21, p53, Valproic Acid


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