1998 Fiscal Year Final Research Report Summary
Research on the potentiators of HSV-specific thymidine kinase for the purpose of their application to gene therapy and antiviral therapy
| Project/Area Number |
09672276
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
HAYASHI Kyoko Toyama Medical and Pharmaceutical University, School of Medicine, Assistant Professor, 医学部, 助手 (60110623)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Toshimitsu Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, 薬学部, 助教授 (40092796)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Gene therapy / Antiviral activity / Herpes simplex virus / Thymidine Kinase (TK) / TK-expressing cell lines / Acyclovir / Ganciclovir / Synergistic effect |
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| Research Abstract |
So far, we found three compounds which exerted synergistic antiherpetic activities with acyclovir (ACV) and ganciclovir(GCV). Especially, of these agents, two diterpenoids, scopadulciol (SDC) and ponicidin (PND), potentiated the cell-killing activity of ACV and GCV in herpes simplex virus type 1(HSV-1) thymidine kinase (TK)-expressing cells. We report about these in detail as follows A naturally occuring flavone, 5,6,7-irimethoxyflavone (TMF), isolated from a plant Gallicarpa japonica, was subjected to antiviral assays . The agent exhibited inhibitory effects on HSV- 1 . TMF and ACV were synergic in their anti-HSV activities, During the evaluation of the effect of ponicidin(PND), which was isolated from a plant Rabdosia ternifolia . on the antiviral activities of ACV and GCV, the compound was found to preferentially activate HSV- 1 -specific TK but not cellular kinases. ln cultured human cancer cells transfected with HSV- 1 TK gene, cytotoxicities of ACV and GCV was strongly potentiated by PND.When the stability of the bioactivity of PND in the blood of mice was determined, the substance showed long-lasting effects on the potentiation of antiherpetic and cytotoxic activities of GCV.Another diterpenoid, SDC isolated from Scoparia dulcis, was also demonstrated as a potentiator of antiherpetic and cell-killing activities of ACV and GCV in in vilro experimental models. These data suggest that combined use of PND or SDC with ACV/GCV will be effective for cancer gene therapy because of more rapid and enhanced tumor elimination.
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