An attempt to develop novel anti-cancer agents through fusion of the cancer stem cell hypothesis and mitochondrial metabolism study

• Project/Area Number: 24650644
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Clinical oncology
• Research Institution: Yamagata University
• Principal Investigator: SEINO Shizuka 山形大学, 医学部, 助手 (80571653)
• Co-Investigator(Renkei-kenkyūsha): SATO Atsushi 山形大学, 医学部, 助教 (30455901)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗がん物質探索 / cancer-initiating cells / oxidative metabolism / mitochondria

Research Abstract

The aim of this project is to test the working hypothesis that Warburg effect plays a critical role in the maintenance of cancer stem cells in various intractable human cancers including malignant brain tumors. The results of a series of experiments revealed that a compound with a mitochondrial respiration-promoting effect inhibits the stemness of cancer stem cells derived from intractable human cancers including malignant brain tumors. The results suggest the possibility that Warburg effect may represent a potential target for cancer stem cell-directed therapy.

Research Products

• [Journal Article] JNK contributes to temozolomide resistance of stem-like glioblastoma cells via regulation of MGMT expression (2014)
  • Author(s): Okada M, Sato A, Shibuya K, Watanabe E, Seino S, Suzuki S, Seino M, Narita Y, Shibui S, Kayama T, Kitanaka C
  • Journal Title: Int J Oncol Volume: 44 Pages: 591-599
  • Peer Reviewed
• [Journal Article] Pivotal role for ROS activation of p38 MAPK in the control of differentiation and tumor-initiating capacity of glioma-initiating cells (2014)
  • Author(s): Sato A, Okada M, Shibuya K, Watanabe E, Seino S, Narita Y, Shibui S, Kayama T, Kitanaka C
  • Journal Title: Stem Cell Res Volume: 12 Pages: 119-131
  • Peer Reviewed
• [Journal Article] Specific role of JNK in the maintenance of the tumor-initiating capacity of A549 human non-small cell lung cancer cells (2013)
  • Author(s): Okada M, Shibuya K, Sato A, Seino S, Watanabe E, Suzuki S, Seino M, Kitanaka C
  • Journal Title: Oncol Rep Volume: 30 Pages: 1957-1964
  • Peer Reviewed
• [Journal Article] Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells (2013)
  • Author(s): Sato A, Okada M, Shibuya K, Watanabe E, Seino S, Suzuki K, Narita Y, Shibui S, Kayama T, Kitanaka C
  • Journal Title: Stem Cell Res Volume: 11 Pages: 601-610
  • Peer Reviewed
• [Journal Article] Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells (2013)
  • Author(s): Sato A et al.
  • Journal Title: Stem Cell Research Volume: 11 Pages: 601-610
  • Peer Reviewed
• [Journal Article] Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK (2012)
  • Author(s): Sato A, Sunayama J, Okada M, Watanabe E, Seino S, Shibuya K, Suzuki K, Narita Y, Shibui S, Kayama T, Kitanaka C
  • Journal Title: Stem Cells Transl Med Volume: 1 Pages: 811-824
  • Peer Reviewed
• [Journal Article] Targeting JNK for therapeutic depletion of stem-like glioblastoma cells (2012)
  • Author(s): Matsuda K, Sato A, Okada M, Shibuya K, Seino S, Suzuki K, Watanabe E, Narita Y, Shibui S, Kayama T, Kitanaka C
  • Journal Title: Sci Rep Volume: 2 Pages: 516-516
  • Peer Reviewed
• [Journal Article] Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK. (2012)
  • Author(s): Sato A et al. (第三著者)
  • Journal Title: Stem Cells Transl Med. Volume: 1 Issue: 11 Pages: 811-24
  • DOI: 10.5966/sctm.2012-0058
  • Peer Reviewed
• [Journal Article] Targeting JNK for therapeutic depletion of stem-like glioblastoma cells (2012)
  • Author(s): Matsuda K, Sato A, Okada M, Shibuya K, Seino S, Suzuki K, Watanabe E, Narita Y, Shibui S, Kayama T, Kitanaka C
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 516-516
  • DOI: 10.1038/srep00516
  • Peer Reviewed
• [Presentation] レスベラトロールによるNanog-p53経路を介したグリオーマ幹細胞の制御 (2013)
  • Author(s): 佐藤篤,岡田雅司,渋谷慶太,清野静香,成田善孝,渋井壮一郎,北中千史,嘉山孝正
  • Organizer: 第14回日本分子脳神経外科学会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2013-10-19
• [Presentation] レスベラトロールによるNanog-p53経路を介したグリオーマ幹細胞の制御 (2013)
  • Author(s): 佐藤篤他
  • Organizer: 第１４回日本分子脳神経外科学会
  • Place of Presentation: パシフィコ横浜（横浜）