Valproic acid inhibits the growth of cervical cancer both in vitro and in vivo.
Valproic acid (VPA), a well-known anti-convulsant, is currently under extensive evaluation as an anti-cancer agent. It is known to exert its anti-cancer 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, 5.0 mM) 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 tumour 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 tumour growth and improved survival advantages in tumour xenografts studies. Furthermore, we also demonstrated that VPA has a direct anti-angiogenic effect in tumour studies and could potentially be a promising candidate for further cervical cancer trails.
College of Life Sciences and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Siraj
S
Sami
Naseruddin
N
Höti
Han-Mei
HM
Xu
Zilong
Z
Shen
Xiaofeng
X
Huang
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry / Q000494:pharmacology; D006657:Histones / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014635:Valproic Acid / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006657:Histones; D014635:Valproic Acid; D006655:Histone Deacetylases