Elucidation of Molecular Mechanism of Cell Death induced by Radiation, Hyperthermia and Ultrasound for Cancer Therapy

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390229
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: University of Toyama
• Principal Investigator: KONDO Takashi 富山大学, 大学院・医学薬学研究部(医学), 教授 (40143937)
• Co-Investigator(Kenkyū-buntansha): TABUCHI Yoshiaki 富山大学, 生命科学先端研究センター, 准教授 (20322109) ; ZHAO Qing-li 富山大学, 大学院・医学薬学研究部(医学), 助教 (90313593) ; TAKASAKI Ichro 富山大学, 生命科学先端研究センター, 助教 (00397176)
• Project Period (FY): 2010 – 2012
• Keywords: 放射線腫瘍学 / 超音波治療学 / 温熱治療学

Research Abstract

Molecular mechanism of cell death induced by ionizing radiation, heat or ultrasound was examined. Stable knockdown of TAK1 caused increase in subG1 fraction and apoptosis induced by X-rays in HeLa cells. Inhibition of DNA-PK increased heat-induced apoptosis in HeLa cells and the knockdown of an identified gene, NR1D1, also enhanced apoptosis. For the cell death induced by ultrasound, cell death signal is modulated by the balance between p53 and Akt via ATM and DNA-PK and the pathway of DNA-PK/Akt is predominant in sonicated cells.

Research Products

• [Journal Article] Utilization of microRNAs whose expression levels decrease in responseto X-ray irradiation for fine-tuning radiation-controlled gene regulation (2013)
  • Author(s): Morii A, Ogawa R, Watanabe A, Cui Z-G, Takasaki I, Doi T, Kondo T, FuseH
  • Journal Title: Int J Mol Med (in press) Pages: 1360
  • DOI: DOI:10.3892/ijmm.2013.1360
  • Peer Reviewed
• [Journal Article] Inactivation of DNA-dependent protein kinase promotes heat-induced apoptosis independently of heat-shock protein induction in human cancer cell lines (2013)
  • Author(s): Okazawa S, Furusawa Y, Kariya A,Hassan MA, Arai M, Hayashi R, TabuchiY, Kondo T, Tobe K
  • Journal Title: PLos One Volume: 8(3) Pages: e58325
  • DOI: DOI:10.1371/journal.pone.0058325
  • Peer Reviewed
• [Journal Article] The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells (2013)
  • Author(s): Yunoki T, Kariya A, Kondo T, Hayashi A, and Tabuchi Y
  • Journal Title: Cancer Lett(inpress) Pages: 049
  • DOI: DOI:10.1016/j.canlet.2013.01.049
  • Peer Reviewed
• [Journal Article] Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation (2013)
  • Author(s): Ogawa R, Morii A, Watanabe A, Cui ZG, Kagiya G, Kondo T, Doi N, and Feril LB Jr
  • Journal Title: Ultrason Sonochem Volume: 20 Pages: 460-467
  • DOI: DOI:10.1016/j.ultsonch.2012.05.007
  • Peer Reviewed
• [Journal Article] TGF-beta-activated kinase 1 promotes cell cycle arrest and cell survival of X-ray-irradiated HeLa cells dependent on p21 induction but independent of NF-kB, p38 MAPK and ERK phosphorylations (2012)
  • Author(s): Furusawa Y, Wei ZL, Sakurai H, Tabuchi Y, Li P, Zhao Q-L, Zhao, Nomura T, Saiki I, and Kondo T
  • Journal Title: Radiat Res Volume: 177 Pages: 766-774
  • DOI: DOI:10.1667/RR2792.1
  • Peer Reviewed
• [Journal Article] Inhibition of checkpoint kinase 1 abrogates G2/M checkpoint activation and promotes apoptosis under heat stress (2012)
  • Author(s): Furusawa Y, Iizumi T, Fujiwara Y, Zhao Q-L, Tabuchi Y, Nomura T, and Kondo T
  • Journal Title: Apoptosis Volume: 17 Pages: 102-112
  • DOI: DOI:10.1007/s10495-011-0660-7
  • Peer Reviewed
• [Journal Article] Mitochondoria -targeted superoxide dismutase (SOD2) regulates radiation resitance and radiation stress response in HeLa cells (2012)
  • Author(s): Hosoki A., Yonekura S.-I., Zhao Q.-L., Wei Z.-L., Takasaki I., Tabuchi Y., Wang L.-L., Hasuike S., Nomura T., Tchibana A., Hashiguchi K., Yonei S., Kondo T., and Zhang-Akiyama Q.-M
  • Journal Title: J Radiat Res Volume: 53 Pages: 58-71
  • DOI: DOI:10.1269/jrr.11034
  • Peer Reviewed
• [Journal Article] NA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines (2012)
  • Author(s): Furusawa Y, Fujiwara Y, Campbell P, Zhao Q-L, Ogawa R, Hassan MA, TabuchiY, Takasaki I, Takahashi A, and KondoT
  • Journal Title: PLoS One Volume: 7 Pages: e29012
  • DOI: DOI:10.1371/journal.pone.0029012
  • Peer Reviewed
• [Journal Article] Ultrasound-induced new cellular mechanism involved in drug resistance (2012)
  • Author(s): Hassan MA, Furusawa Y, Minemura M, Rapoport N, Sugiyama T, and Kondo T
  • Journal Title: PLoS One Volume: 7 Pages: e48291
  • DOI: DOI:10.1371/journal.pone.0048291
  • Peer Reviewed
• [Journal Article] Inhibition of DNA-dependent protein kinase promotes ultrasound -induced cell death including apoptosis in human leukemia cells (2012)
  • Author(s): Furusawa Y, Fujiwara Y, Hassan MA, Tabuchi Y, Morita A, Enomoto A,and Kondo T
  • Journal Title: Cancer Lett Volume: 322 Pages: 107-112
  • DOI: DOI:10.1016/j.canlet.2012.02.020
  • Peer Reviewed
• [Journal Article] Ultrasound activates ataxia telangiectasia mutated- and Rad-3 related (ATR)-checkpoint kinase 1 (Chk1) pathway in human leukemia Jurkat cells (2012)
  • Author(s): Furusawa Y, Iizumi T, Fujiwara Y, Hassan MA, Tabuchi Y, Nomura T, and Kondo T
  • Journal Title: Ultrason Sonochem Volume: 19 Pages: 1246-1251
  • DOI: DOI:10.1016/j.ultsonch.2012.04.003
  • Peer Reviewed
• [Journal Article] Regulation of gene expression in prostate cancer cells with an artificially constructed promoter responsive to radiation (2012)
  • Author(s): Morii A, Ogawa R, Watanabe A, Kakutani S, Zhao Q-L, Kume K, Kondo T, and Fuse H
  • Journal Title: Gene Ther Volume: 19 Pages: 219-227
  • DOI: DOI:10.1038/gt.2011.89
  • Peer Reviewed
• [Journal Article] Enhanced gene transfection using calcium phosphate co-precipitates and low-intensity pulsed ultrasound (2012)
  • Author(s): Hassan MA, Ahmed IS, Campbell P, Kondo T
  • Journal Title: Eur J Pharmaceut Sci Volume: 47 Pages: 768-773
  • DOI: DOI:10.1016/j.j.ejps.2012.08.007
  • Peer Reviewed
• [Presentation] Roles of intracellular oxidative stress in DNA Damage and apoptosis induced by different physical stressors; ionizing radiation, hyperthermia and ultrasound (2012)
  • Author(s): Kondo T, Hassan MA, Zhao QL, Ogawa R, Tabuchi Y, and Furusawa Y
  • Organizer: 28th RBC-NIRS International Symposium, Radiationassociated Repair Proteins and DNA Repair Network
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20121129-30
• [Presentation] Roles of intracellular oxidative stress in the enhancement of hyperthermia-induced apoptosis. (ASHO award Lecture) (2012)
  • Author(s): Kondo T
  • Organizer: The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
  • Place of Presentation: Kyoto
  • Year and Date: 20120828-31
• [Book] Chapter 12: Sonodynamic Therapy in Therapeutic Ultrasound: Mechanisms to Applications (Public Health in the 21st Century) (2011)
  • Author(s): Feril LB Jr., Tachibana K, Kondo T, and Campbell P
  • Total Pages: V. 279-295
  • Publisher: Editor, Frenkel V. 279-295, Nova Science Publishers, Inc
• [Book] Ultrasound-induced DNA damage and signal transductions indicated by gamma H2AX (2011)
  • Author(s): Furusawa Y, Fijiwara Y, Zhao Q-L, Hassan MA, Ogawa R, Tabuchi Y, Takasaki I,Takahashi A, Ohnishi T, and Kondo T
  • Publisher: 10th International Symposium on Therapeutic Ultrasound (ISTU2010) Editors, Matsumoto Y, Crum LA, and ter Haar GR, 322-325, AIP Conf Proc 1359, American Institute of Physics
• [Remarks]
  • URL: http://www.med.u-toyama.ac.jp/radsci/index.html