Identification of radiosensitizers targeting cancer stem cells in cervical cancer by using high throughput screening

• Project/Area Number: 26670559
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Osaka University
• Principal Investigator: Tamari Keisuke 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (30718995)
• Co-Investigator(Kenkyū-buntansha): SEO Yuji 大阪大学, 医学系研究科, 特任助教 (00302000) ; ISOHASHI Fumiaki 大阪大学, 医学系研究科, 特任准教授 (00448036) ; OGAWA Kazuhiko 大阪大学, 医学系研究科, 教授 (40253984) ; HAYASHI Kazuhiko 大阪大学, 医学系研究科, 招へい教員 (70718981)
• Co-Investigator(Renkei-kenkyūsha): ISHII Hideshi 大阪大学, 医学系研究科, 特任教授 (10280736) ; Kim Yoon-Jeong 大阪大学, 産学連携本部, 教授 (40574330)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 放射線増感剤 / 化合物スクリニーニング / 放射線治療 / 癌幹細胞 / 創薬 / 放射線増感

Outline of Final Research Achievements

Cancer recurrence and metastases can be due to a subpopulation of cells with stem-like characteristics, cancer stem cells (CSCs) which maintain the capacity to regenerate entire tumors. We suspected that CSC-specific compounds had radiosensitizing effects in parental cells. To accomplish this purpose, we performed high throughput screening (HTS) to identify compounds that specifically act CSCs. Finally, we found five CSC-specific compounds. However, these compounds had no significant radiosensitizing effects for parental HeLa cells. We also performed cell-based high throughput screening to study new radiosensitizers targeting hypoxic tumor cells. We identified 22 compounds as candidate. Clonogenic survival assay showed their significant radiosensitizing effect in hypoxic condition. In conclusion, we identified new radiosensitizers by high throughput screening. This is a possible method for identifying radiosensitizers targeting hypoxic cancer cells.

Research Products

• [Presentation] A novel method to identify radiosensitizers targeting hypoxic cancer cells by high throughput screening (2016)
  • Author(s): Tamari K, Seo Y, Takahashi Y, Suzuki O, Isohashi F, Yoshioka Y, and Ogawa K.
  • Organizer: AACR Annual Meeting 2016
  • Place of Presentation: Ernest N. Morial Convention Center New Orleans, Louisiana
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Identification of novel radiosensitizers targeting hypoxic cancer cells by high throughput screening (2016)
  • Author(s): Tamari K, Seo Y, Takahashi Y, Suzuki O, Isohashi F, Yoshioka Y, and Ogawa K.
  • Organizer: Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
  • Place of Presentation: Hyatt Regency Maui Maui, Hawaii
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Identification of radiosensitizers targeting cancer stem cells in cervical cancer by using high throughput screening. (2015)
  • Author(s): Tamari K, Ishii H, Konno M, Nishida N, Kawamoto K, Koseki J, Beak SJ, Taketo K, Doki Y, Mori M, Ogawa K.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08