title: Anticancer effects of valproic acid on oral squamous cell carcinoma via SUMOylationin vivoandin vitro.
abstract: Aberrant histone deacetylase (HDAC) has a key role in the neoplastic process associated with the epigenetic patterns of tumor-related genes. The present study was performed to investigate the effects and determine the mechanism of action of the HDAC inhibitor, valproic acid (VPA), on the CAL27 cell line derived from oral squamous cell carcinoma (OSCC). The effects of VPA on the viability of CAL27 cells were investigated using MTT assays. Alterations in the cell cycle and apoptosis were also examined using propidium iodide (PI) and Annexin V-PI assays, and were subequently analyzed by flow cytometry. Small ubiquitin-related modifier (SUMO)-related genes were evaluated by reverse transcription-quantitative polymerase chain reaction analysis. In addition, the effects of VPA were assessed using a xenograft modelin vivo. The present results demonstrated significant dose-dependent inhibition of cell viability following VPA treatment. Treatment with VPA increased the distribution of CAL27 cells in the G1phase and reduced cells in the S phase, and significantly increased the expression levels of SUMO1 and SUMO2 (P<0.01). Using a xenograft model, the mean tumor volume in VPA-treated animals was demonstrated to be significantly reduced, and the rate of apoptosis was significantly increased, as compared with the control animals. These results suggested that VPA may regulate SUMOylation, producing an anticancer effectin vivo. Further investigation into the role of VPA in tumorigenesis may identify novel therapeutic targets for OSCC.
authors.affiliation: Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Sang
authors.affiliation: Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Yu
keywords: CAL27 cells; histone deacetylase; oral squamous cell carcinoma; small ubiquitin-related modifier; valproic acid