Analysis of cell cycle related signals for inhibition of histone acetylation in pancreatic cancer cells

• Project/Area Number: 16H06773
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ONO Hiroaki 東京医科歯科大学, 医学部附属病院, 助教 (60466901)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膵臓癌 / 細胞周期 / 抗がん剤 / 腫瘍外科 / 分子細胞学

Outline of Final Research Achievements

Histone Acetylation plays a significant role in DNA replication and regulation of cell cycle. We tried to investigate its relationship between Histone acetylation and cell cycle especially in pancreatic cancer. Our study has shown evidence that Histone acetylation such as H3K9Ac and H3K27Ac is activated in pancreatic cancer cell lines. Furthermore, C646, which is a biological inhibitor of Histone acetylation, inhibited cell cycle and induced cell apoptosis of pancreatic cancer cell lines as well. Cell cycle related genes of cyclin B1 and CDC2 were also inhibited by C646 treatment. These data suggested that down-regulation of Histone acetylation induced G2/M cell cycle arrest through inhibition of cell cycle related genes at transcriptional level.

Research Products

• [Int'l Joint Research] ミシガン州立大学外科(米国)
• [Journal Article] C646 inhibits G2/M cell cycle-related proteins and potentiates anti-tumoreffects in pancreatic cancer (2021)
  • Author(s): Hiroaki Ono, Tomotaka Kato, Yoshiki Murase, Yutaro Nakamura, Yoshiya Ishikawa, Shuichi Watanabe, Keiichi Akahoshi, Toshiro Ogura, Kosuke Ogawa, Daisuke Ban, Atsushi Kudo, Yoshimitsu Akiyama, Shinji Tanaka, Hiromichi Ito, Minoru Tanabe
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 10078-10078
  • DOI: 10.1038/s41598-021-89530-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer (2016)
  • Author(s): Hiroaki Ono
  • Journal Title: Oncotarget Volume: 7 Issue: 32 Pages: 51301-51310
  • DOI: 10.18632/oncotarget.10117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ヒストンアセチル基転移酵素阻害剤 C646 はG2/M細胞周期停止を介し膵臓癌細胞株に おける細胞増殖を抑制する (2017)
  • Author(s): 小野宏晃 伊藤寛倫 稲澤譲治 田邉稔
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] ヒストンアセチル化阻害による膵臓癌の細胞 周期とジェムザール感受性への影響と解析 (2017)
  • Author(s): 小野宏晃 Marc Basson 田邉稔 伊藤寛倫
  • Organizer: 第48回日本膵臓学会