1997 Fiscal Year Final Research Report Summary
Establishment of screening systems that detect chemicals against circulatory diseases using redox changes as an indicator.
| Project/Area Number |
07557374
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | SHOWA UNIVERSITY |
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Principal Investigator |
NOSE Kiyoshi (Showa Univ.Sch.Pharm.Sci., Professor), 薬学部, 教授 (70012747)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Toshiharu (Meiji Institute of Health, Vice president), 副所長
YAMAMOTO Toshinori (Showa Univ.Sch.Pharm.Sci., Professor), 薬学部, 教授 (30112741)
MASHIMO Jun'ichi (Showa Univ.Sch.Pharm.Sci., Research Associate), 薬学部, 助手 (60054045)
EGAWA Kiyoshi (Showa Univ.Sch.Pharm.Sci., Lecturer), 薬学部, 講師 (00095879)
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| Project Period (FY) |
1995 – 1997
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| Keywords | WAFl / p21 / drug screening systems / luciferase / Spl transcription factor / anti-cancer drugs |
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| Research Abstract |
The WAF1/p21 is one of target genes of tumor suppressor p53 that is regulated through redox-based mechanisms. Assay systems were constructed using WAF1/p21 gene enhancer and luciferase as reporters. DNA fragments of human p21 gene 5'-upstream -2400 bp and -210 bp were ligated to the luciferase gene, and plasmids were introduced into p53-deficient Saos-2 or p53-mutated TMK-l cells. Stable lines that express luciferase in response to activator of p21 gene (butyrate) established and used for the screening. Among 1300 culture broths of Streptomyces, three active substances were detected and identified as Actinomycin D analogue, phleomycin and trichostatin A.These substances induced p21 gene expression in p53-independent manner, and transcriptional elements for the induction were revealed to be the Spl elements that localize -150 bp from the cap sites. Further screening will detect novel substances that are useful as anti-tumorigenic or anti-fungal drugs.
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