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THE ROLE OF REACTIVE OXYGEN INTERMEDIATES AND THEIR SCAVENGERS ON APOPTOSIS INDUCTION OF SQUAMOUS CELL CARClNOMA CELLS

Research Project

Project/Area Number 10671769
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionKochi Medical School

Principal Investigator

YONEDA Kazunori  Kochi Medical School, Department of Oral Surgery, Associate Professor, 医学部, 助教授 (90182849)

Co-Investigator(Kenkyū-buntansha) OSAKI Tokio  Kochi Medical School, Department of Oral Surgery, Professor, 医学部, 教授 (70031995)
UETA Eisaku  Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部・附属病院, 助手 (10203431)
YAMAMOTO Tetsuya  Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部・附属病院, 講師 (00200824)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordssquamous cell carcinoma cells / apoptosis / reactive oxygen intermediates / HィイD22ィエD2OィイD22ィエD2 / Mn-SOD / LAK cells
Research Abstract

To induce apoptosis sufficient for cancer control, we investigated the role of reactive oxygen intermediates (ROI) and their scavengers in induction of apoptosis of squamous cell carcinoma (SCC) cells. The results obtained are as follows ;
1, The SCC lines, which were established from oral SCCs, revealed almost same activities of catalase, gluthatione peroxidase, and Cu, Zn-superoxide dismutase (SOD). However, Mn-SOD activities differed largely among the cell lines.
2, SCC lines with a high Mn-SOD activity were more resistant to 5-FU and γ-rays than those with a low Mn-SOD activity, and the Mn-SOD activities were inversely correlated with apoptosis by 5-FU and γ-rays.
3, Apoptosis was closely correlated with the intracellular and intra-mitochondrial ROI (HィイD22ィエD2OィイD22ィエD2) levels, which were parallel with the decrease of mitochondrial membrane potential, release of cytochrome c, caspase-3 activation, and DNA fragmentation.
4, By treatment with 5-FU and γ-rays, Mn-SOD-mRNA expression and Mn-SOD activities were increased in all SCC lines.
5, Mn-SOD-antisense-transfected SCC cells were more strongly induced to apoptosis after treatment with 5-FU and γ -rays compared with wild SCC cells.
6, Subcutaneous tumors in nu/nu mice, in which Mn-SOD-antisense-transfected SCC cells were transplanted, were more sensitive to γ-rays and 5-FU than tumors of non-transfected SCC cells.
These results indicate that ROI play an important role in apoptosis induced by 5-FU and γ-rays and that among the ROI scavengers, Mn-SOD is the strongest inhibitor of apoptosis. Therefore, as the effective SCC therapy, inactivation of ROI scavengers, especially, Mn-SOD, is proposed.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Kazunori Yoneda: "The inhibitory action of BOF-A2,a 5-fluorouracil derivative,on squamous cell carcinoma"Cancer Letters. 137・1. 17-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eisaku Ueta: "Manganese superoxide dismutase negatively regulates the induction of apoptosis by 5-fluorouracil,peplomycin and γ-rays in squamous cell carcinoma cells"Japanese Journal of Cancer Research. 95・5. 555-564 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokio Osaki: "Diffuse mode of tumor cell invasion and expression of p53 ptotein but not of p21 protein are correlated with control failure in oral carcinoma and their metastasis foci"Oncology. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "The inhibitory action of BOF-A2, a 5-fluorouracil derivative, on squamous cell carcinoma"Cancer Letters. 137(1). 17-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eisaku Ueta: "Manganese superoxide dismutase negatively regulates the induction apoptosis by 5-fluorouracil, peplomycin and γ-rays in squamous cell carcinoma cells"Japanese Journal of Cancer Research. 90(5). 555-564 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokio Osaki: "Diffuse mode of tumor cell invasion and expression of p53 protein but not of p2 1 protein are correlated with control failure in oral carcinoma and their metastasis foci."Oncology. in press. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "The inhibitory action of BOF-A2,a 5-fluorouracil derivative,on squamous cell carcinoma"Cancer Letters. 137・1. 17-25 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Eisaku Ueta: "Manganese superoxide dismutase negatively regulates the induction of apoptosis by 5-fluorouracil,peplomycin and γ-rays in squamous cell carcinoma cells"Japanese Journal of Cancer Research. 90・5. 555-564 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokio Osaki: "Diffuse mode of tumor cell invasion and expression of p53 protein but not of p21 protein are correlated with control failure in oral carcinoma and their metastasis foci."Oncology. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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