Effects of anti-angiogenesis by HDAC inhibitor and DNA methylation inhibitor

2012 Fiscal Year Final Research Report

• Project/Area Number: 23792159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hyogo Medical University
• Principal Investigator: YAMANEGI Koji 兵庫医科大学, 医学部, 講師 (00434944)
• Project Period (FY): 2011 – 2012
• Keywords: 骨肉腫、 / HDAC inhibitor、 / DNA methylation inhibitor、 / 腫瘍血管新生

Research Abstract

We investigated the effects of anti-angiogenesis by valproic acid (VPA) (HDAC inhibitor) in combination with hydralazine (Hy) (DNA methylation inhibitor) on U-2 OS and SaOS-2 human osteosarcoma cells. Vascular endothelial growth inhibitor (VEGI) are potent inhibitors to suppress endothelial cell proliferation, angiogenesis, also tumor growth and neovascularization. These inhibitions are mediated by death receptor 3 (DR3) which induces apoptosis, and its function is blocked by decoy receptor 3 (DcR3). VPA increased VEGI expression and Hy increased DR3 expression. Their combination induced further increasing effect of both VEGI and DR3 without induction of DcR3 on osteosarcomas and human microvascular endothelial cells. Furthermore, VPA treated medium of osteosarcoma cells can inhibit tube formation in vitro. Thus, these results, together, suggest that VPA and Hy are considered to be one of the promising strategies in the development of novel anticancer therapy.

Research Products

• [Journal Article] Decreased expression of VE-cadherin and claudin-5 and increased phosphorylation of VE-cadherin in vascular endothelium in nasal polyps (2013)
  • Author(s): Yukitatsu Y, Hata M, Yamanegi K, Yamada N, Ohyama H, Nakasho K, Kojima Y, Oka H, Tsuzuki K, Sakagami M, Terada N.
  • Journal Title: Cell Tissue Res. Volume: 352 Pages: 647-657
  • DOI: doi:10.1007/s00441-013-1583-0
  • Peer Reviewed
• [Journal Article] Phenotypic characteristics and proliferative activity of hyperplastic ductule cells in cholangiofibrosis induced by thioacetamide in rats (2013)
  • Author(s): Hata M, Iida H, Yamanegi K, Yamada N, Ohyama H, Hirano K, Nakasho K and Terada N.
  • Journal Title: Exp Toxicol Pathol. Volume: 65 Pages: 351-356
  • DOI: doi:10.1016/j.etp.2011.11.004.
  • Peer Reviewed
• [Journal Article] Down-regulation of matrix metalloproteinase-9 mRNA by valproicacid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the cell-surface of human osteosarcoma cells (2012)
  • Author(s): Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho N, Yamada N, Hata M, Fukunaga S, Futani H, Okamura H and Terada N.
  • Journal Title: Oncol Rep. Volume: 28 Pages: 1585-1590
  • DOI: doi:10.3892/or.2012.1981.
  • Peer Reviewed
• [Journal Article] Fukunaga S, Futani H, Okamura H and Terada N., Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death (2012)
  • Author(s): Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho N, Yamada N, Hata M
  • Journal Title: Int J Oncol. Volume: 41 Pages: 83-91
  • DOI: doi:10.3892/ijo.2012.1438.
  • Peer Reviewed
• [Journal Article] Expression of carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma (2012)
  • Author(s): Itoyama M, HaTa M, Yamanegi K, Yamada N, Ohyama H, Hirano K, Terada N and Nakasho K.
  • Journal Title: Med Mol Morpol. Volume: 45(1) Pages: 7-13
  • DOI: doi:10.1007/s00795-010-0534-z.
  • Peer Reviewed
• [Journal Article] The promotional effect of IL-22 on mineralization activity of periodontal ligament cells (2012)
  • Author(s): Kato-Kogoe N, Nishioka T, Kawabe M, Kataoka F, Yamanegi K, Yamada N, Hata M, Yamamoto T, Nakasho K, Urade M, Terada N, Ohyama H.
  • Journal Title: Cytokine. Volume: 59 Pages: 41-48
  • DOI: doi:10.1016/j.cyto.2012.03.024.
  • Peer Reviewed
• [Journal Article] Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner (2012)
  • Author(s): Yamada N, Yamanegi K, Ohyama H, Hata M, Nakasho K, Futani H, Okamura H, Terada N.
  • Journal Title: Int J Oncol. Volume: 41 Pages: 2005-2012
  • DOI: doi:10.3892/ijo.2012.1630.
  • Peer Reviewed
• [Journal Article] Expression of hepatocyte markers in mass-forming peripheral and periductal-infiltrating hilar intrahepatic cholangiocarcinomas (2011)
  • Author(s): Iida H, Hata M, Kakuno A, HiranoH, Yamanegi K, Yamada N, Ohyama H, Terada N, Yasui C, Yamanaka N and Nakasho K.
  • Journal Title: Oncol Letters. Volume: 2 Pages: 1041-1046
  • DOI: doi:10.3892/ol.2011.405
  • Peer Reviewed
• [Journal Article] a repository for human cell information for cell studies and differentiation analyses (2011)
  • Author(s): Hatano A, Chiba H, Moesa HA, Taniguchi T, Nagaie S, Yamanegi K, Takai-Igarashi T, Tanaka H and Fujibuchi W., CELLPEDIA
  • Journal Title: Database
  • DOI: doi:10,1093/database/bar046.
  • Peer Reviewed
• [Presentation] エナメル上皮腫術後再発悪性転化を疑った症例 (2012)
  • Author(s): 山根木康嗣、大山秀樹、和唐雅博、富永和也、益野一哉、国分麻佑、嘉藤弘仁、西川哲成、田中昭男
  • Organizer: 第23回日本臨床口腔病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-08-30
• [Presentation] ヒストン脱アセチル化阻害剤を用いた腫瘍血管新生抑制 (2012)
  • Author(s): 山根木康嗣、小林健太、中正恵二、大山秀樹、山田直子、秦正樹、寺田信行
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-28
• [Presentation] Th17細胞産生性サイトカインが血管石灰化に及ぼす影響 (2012)
  • Author(s): 大山秀樹、片岡芙紗、川辺睦記、小越菜保子、山根木康嗣、山田直子、秦正樹、中正恵二、寺田信行
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-28
• [Presentation] 肝内胆管嚢胞性腫瘍の2例 (2012)
  • Author(s): 中正恵二、山根木康嗣、大山秀樹、平野博嗣、山田直子、秦正樹、寺田信行
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] チオアセトアミド誘導ラット肝胆管様管状構造における胆管上皮細胞および肝細胞形質発現と細胞増殖能の検討 (2012)
  • Author(s): 秦正樹、山根木康嗣、山田直子、大山秀樹、平野博嗣、寺田信行、中正恵二
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] Comprehensive human cell database toward cell differentiation analysis (2012)
  • Author(s): Hatano, A., Chiba, H., Taniguchi, T., Yamanegi, K., Takai, T., Tanaka, H., Fujibuchi, W., CELLPEDIA
  • Organizer: Systems Biology : Global regulation of gene expression
  • Place of Presentation: New York, USA
  • Year and Date: 2012-03-22
• [Presentation] Effective inhibition of postoperative pulmonary metastasis of osteosarcoma cells by a combination of ifosfamide and interleukin-18 (2011)
  • Author(s): Yamada N, HataM, Yamanegi K, Ohyama H, Nakasho K, Futani H, Okamura H, Terada N
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] 細胞分化解析を目指した網羅的ヒト細胞データベース「CELLPEDIA」 (2011)
  • Author(s): 幡野晶子、千葉啓和、谷口丈晃、山根木康嗣、高井貴子、田中博、藤渕航
  • Organizer: 2011統合データベースシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-10-05
• [Presentation] ヒストン脱アセチル化阻害剤の癌細胞に及ぼす効果 (2011)
  • Author(s): 山根木康嗣
  • Organizer: 第54回日本病理学会近畿支部学術集会(平成22年度公募部門学術奨励賞受賞講演)
  • Place of Presentation: 兵庫
  • Year and Date: 2011-09-10
• [Presentation] 左舌口底部腫瘍の1例 (2011)
  • Author(s): 山根木康嗣、大山秀樹、和唐雅博、富永和也、国分麻佑、嘉藤弘仁、益野一哉、西川哲成、田中昭男
  • Organizer: 第22回日本臨床口腔病理学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2011-08-24