New developments in mitochondrial study to overcome

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659174
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tohoku University
• Principal Investigator: FUKUMOTO MANABU 東北大学, 加齢医学研究所, 教授 (60156809)
• Co-Investigator(Renkei-kenkyūsha): KUWAHARA Yoshikazu 東北大学, 加齢医学研究所, 助教 (00392225) ; SHIMURA Tsutomu 国立保健医療科学院, 生活環境研究部, 上席主任研究官 (40463799)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 臨床的放射線耐性 / がん細胞 / ミトコンドリア / ワールブルグ効果

Research Abstract

Mitochondrial reactive oxygen species (ROS) was detectable in parental cells but not in clinically relevant radioresistant (CRR) cells after 10 Gy of X-ray irradiation or 100 ng/ml of docetaxel (DTX) treatment. We established cells resistant to H2O2 and they revealed to be resistant both to X-rays and DTX. Mitochondrial DNA depleted rho0 cells were also established. They were resistant both to X-ray irradiation and DTX treatment without ROS production. Theses suggest that ROS derived from mitochondria are involved in the CRR phenotype and DTX resistance.

Research Products

• [Journal Article] Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors (2014)
  • Author(s): Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T, Mori S, Echigo S, Ohkubo Y, Fukumoto M.
  • Journal Title: Cancer Med
  • DOI: 10.1002/cam4.185
  • Peer Reviewed
• [Journal Article] Hypothermia protects against fulminant hepatitis in mice by reducing reactive oxygen species production (2013)
  • Author(s): Sakurai T, Kudo M, Watanabe T, Itoh K, Higashitsuji H, Arizumi T, Inoue T, Hagiwara S, Ueshima K, Nishida N, Fukumoto M, Fujita J.
  • Journal Title: Dig Dis Volume: 31(5-6) Pages: 440-6
  • DOI: 10.1159/000355242
  • Peer Reviewed
• [Journal Article] The role of cyclin D1 in response to long-term exposure to ionizing radiation (2013)
  • Author(s): Shimura T, Fukumoto M, Kunugita N.
  • Journal Title: Cell Cycle Volume: 1;12(17) Pages: 2738-43
  • DOI: 10.4161/cc.25746
  • Peer Reviewed
• [Journal Article] Cyclin D1 overexpression perturbs DNA replication and induces replication-associated DNA double-strand breaks in acquired radioresistant cells (2013)
  • Author(s): Shimura T , Ochiai Y, Noma N, Oikawa T, Sano Y, Fukumoto M.
  • Journal Title: Cell Cycle Volume: 1;12(5) Pages: 773-82
  • DOI: 10.4161/cc.23719
  • Peer Reviewed
• [Journal Article] Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-1 (2013)
  • Author(s): Liu Y, Higashitsujia H, Higashitsuji Hi, Itoh K, Sakurai T, Koike K, Hirota K, Fukumoto M, Fujita J.
  • Journal Title: Biochem Biophys Res Commun Volume: 432(1) Pages: 22-7
  • DOI: 10.1016/j.bbrc.2013.01.093
  • Peer Reviewed
• [Journal Article] Activation of the AKT/cyclin D1/Cdk4 survival signaling pathway in radioresistant cancer stem cells (2012)
  • Author(s): Shimura T, Noma N, Oikawa T, Ochiai Y, Kakuda S, Kuwahara Y, Takai Y, Fukumoto M.
  • Journal Title: Oncogenesis Volume: 1 Pages: e12
  • DOI: 10.1038/oncsis
  • Peer Reviewed