Potentiation of ganciclovir toxicity in the herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin

	Potentiation of ganciclovir toxicity in the herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin
	Hayashi, K ; Hayashi, T ; Sun, HD; Takeda, Y
	2000
发表期刊	CANCER GENE THERAPY
卷号	7 期号:1 页码:45-52
摘要	The herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (CCV) administration system is commonly used in gene therapy trials. We have evaluated the effect of ponicidin, a diterpenoid isolated from a plant, Rabdosia ternifolia, on the cell-killing activity of the anti-herpes drugs acyclovir (ACV) and CCV. Ponicidin preferentially activated HSV-1-specific TK but not cellular kinases. In HSV-infected cells, ponicidin significantly accumulated the phosphorylated metabolites of CCV and suppressed the extracellular release of CCV. These data suggested that the cytotoxicities of ACV and CCV in HSV-TK-expressing cells might be potentiated by ponicidin. After transfected with the HSV-1 TK gene, COS-1 and several human cancer cells became highly sensitive to the cytotoxic properties of the nucleoside analogs. When ponicidin at the concentration without antiviral activities (0.2 mu g/mL) was combined with ACV or GCV, the cytotoxic levels in HSV-TK-expressing cells were enhanced by 3- to 87-fold and 5- to 52-fold, respectively, compared with the nucleoside alone. When the stability of the bioactivity of ponicidin in the blood of mice was evaluated, the substance showed relatively long-lasting effects on the potentiation of the anti-herpetic and cytotoxic activities of GCV after intravenous administration. These data suggest that the combined use of ponicidin with CCV will be effective for cancer gene therapy, because high cytotoxicity in viral TK-expressing cells should yield more rapid and enhanced tumor elimination.
关键词	Herpes Simplex Virus Type 1 Thymidine Kinase Transfected Tumor Cells Cytotoxicity Combination Therapy
收录类别	SCI
语种	英语
WOS记录号	WOS:000085401500006
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/23965
专题	植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.Toyama Med & Pharmaceut Univ, Dept Virol, Toyama 9300194, Japan 2.Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan 3.Acad Sinica, Kunming Inst Bot, Kunming 650107, Yunnan, Peoples R China 4.Univ Tokushima, Fac Integrated Arts & Sci, Tokushima 770, Japan
推荐引用方式 GB/T 7714	Hayashi, K,Hayashi, T,Sun, HD,et al. Potentiation of ganciclovir toxicity in the herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin[J]. CANCER GENE THERAPY,2000,7(1):45-52.
APA	Hayashi, K,Hayashi, T,Sun, HD,&Takeda, Y.(2000).Potentiation of ganciclovir toxicity in the herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin.CANCER GENE THERAPY,7(1),45-52.
MLA	Hayashi, K,et al."Potentiation of ganciclovir toxicity in the herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin".CANCER GENE THERAPY 7.1(2000):45-52.

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