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Tumor Biology

, Volume 32, Issue 2, pp 335–346 | Cite as

The G1 phase arrest and apoptosis by intrinsic pathway induced by valproic acid inhibit proliferation of BGC-823 gastric carcinoma cells

  • Xia Zhao
  • Weihua Yang
  • Changwen Shi
  • Wanshan Ma
  • Jianing Liu
  • Yunshan Wang
  • Guosheng Jiang
Research Article

Abstract

Recent studies have demonstrated that the histone deacetylation level was closely related to the genesis and development of tumors. Thus, activating histone acetyltransferases and/or suppressing histone deacetylases (HDACs) can become an approach for tumor chemotherapy. The histone acetylation regulation often results in the inhibition of cell proliferation, induction of cell apoptosis or differentiation, and cell cycle arrest in G1 phase. It has been demonstrated recently that the traditional anticonvulsant valproic acid was an efficient class I HDAC inhibitor (HDACI); however, its antitumor effect and mechanisms on gastric cancers so far has not been elucidated clearly. In the present study, gastric carcinoma cell lines BGC-823, HGC-27, and SGC-7901 were cultured with valproic acid (VPA) in vitro. The cell morphology was observed by invert microscope, the proliferation was detected by MTT assay, the apoptosis and cell cycle were analyzed by flow cytometry assay with Annexin V/PI and PI, the activities and protein expressions of Caspase 3, Caspase 8, Caspase 9 of BGC-823 cells were detected by spectrophotometry and indirect immunofluorescence technique, respectively. The protein expressions of Cyclin A, Cyclin D1, Cyclin E, P21Waf/cip1 of BGC-823 cells were analyzed by indirect immunofluorescence assay, and messenger ribonucleic acid (mRNA) expressions were detected by RT-PCR assay. The results showed that the proliferation of three kinds of gastric carcinoma cells could be inhibited obviously by VPA, which was related to the apoptosis induction and cell cycle arrest in G1 phase. The intrinsic pathway (cytochrome C pathway) was chiefly involved in the mechanism of apoptosis, which was indicated by activation of Caspase 9 and Caspase 3. The extrinsic pathway was partially involved, with slight activation of Caspase 8. The mechanism underlying its effect on cell cycle arrest in G1 phase induction was due to the upregulation of P21Waf/cip1, Mad1 expression and downregulation of Cyclin A, c-Myc expression.

Keywords

Histone deacetylase Histone deacetylase inhibitor BGC-823 gastric carcinoma cell Valproic acid (VPA) Apoptosis 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  1. 1.The Central LaboratoryQianfoshan Hospital of Shandong ProvinceJinanChina
  2. 2.Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Medical Laboratory for Tumor Immunology and Chinese Medicine Immunology of Shandong Province, Key Laboratory for Rare and Uncommon Diseases of Shandong ProvinceThe Institute of Basic Medicine, Shandong Academic of Medical SciencesJinanChina
  3. 3.The Central LaboratoryJinan Central HospitalJinanChina

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