| Project/Area Number |
12470125
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
NIITSU Yoshiro Sapporo Medical University, School of medicine, professor, 医学部, 教授 (10045502)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Hiroshi TEIJIN PHARMACUITICAL INC. manager, 創薬第二研究所・創薬化学グループ, 統轄
TAKAYAMA Tetsuji Sapporo Medical University, School of medicine, assistant professor, 医学部, 講師 (10284994)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2001: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | GST-π / ACF / Colorectal cancer / Chemoprevention / グルタチオンアナログ |
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| Research Abstract |
Aim: We synthesized a new glutathione analogue, a specific inhibitor for Glutathione Stransferase (GST)-π, and examined the chemopreveritive effect on colon carcinogenesis of rat. We also examined if glutathione analogue induce apoptosis in human ACF, a precursor of adenoma-carcinoma sequence. Methods and Results: (1)Selective inhibitor of GST-π, ν-glutamyl-S-(benzyl) cyteinyl phenlyglycine diethyester, was synthesized and purified by HPLC. (2) 20 mg/kg of azoxymethane was injected (day1, i. p.) in rat and.the glutathione analogue was administered (30 mg kg, I.p.) for 3 weeks (day1- 21). The number of ACF in rats treated with glutathione analogue and control rats were 9.8 ± 2.2 and 22.5 ± 4.5, respectively. There was a significant difference between the two groups (p<0.01). (3) Biopsy specimens of ACF were treated with glutathione analogue (10-50μM) in the presence of DCA(1mM) and the TUNEL staining was performed. The percentages of apoptotic cells with glutathione analogue (14.8±4.3%) was significantly higher than that without it (4.2 ± 2.3 %). (4) Acute toxicity of glutathione analogue in mice was examined, and the values of LD 50 were very high (700 - 1000 mg/kg). Conclusion: It was demonstrated that glutathione analogue is a promising chemopreventive agent for colon carcinogenesis.
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