MECHANISM OF INDUCTION OF DIFFRENTIATION INLEUKEMIA CELLS BY TOPOISOMERASE INHIBITORS
拓扑异构酶抑制剂诱导白血病细胞分化的机制
基本信息
- 批准号:03671063
- 负责人:
- 金额:$ 1.34万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (C)
- 财政年份:1991
- 资助国家:日本
- 起止时间:1991 至 1993
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Camptothecin and VP16 are known as inhibitors for topoisomerase I and II, respectively. We have previously found that these topoisomerase inhibitors and bufalin, an active principle of the Chinese medicine chan'su, induce differentiation of various kinds of human leudemia cell lines. The present study was undertaken to investigate the mechanism og the induction of differintiation in human leukemia cells by these differentiationinducers. Bufalin indirectly inhibits topoisomerase II in leukemia HL60 cells via signal transduction pathway. Therefore, bufalin is classified as a movel inhibitor of topoisomerasa II.All these topoisomerase inhibitors arresred the cell cycle of leukemia cells at the G2/M phase. Synergistic effects on the induction of differentiation in leukemia cells were observed by combination of bufalin with camptothecin or VP16. Combination of retinoic acid, clinically used as a drug for acute promyelocytic leukemia, with camptothecin or VP16 also showed marked synergistic effects on the differentiation of leukemia cells. Although camptothecin and VP16 are known as inducers of apoptosis, we found that bufalin can also induce apoptosis in HL60 cells when used at higher concentrations than used for inducing differentiation. Synergistic effects on the induction of apoprosis were observed by combined teratment of camptothecin with VP16, retinoic acid with VP16, or bufalin with retinoic acid. These results suggest the usefulness of these topoisomerase ingibitors for diffentiation-apoptosis inducing therapy for cancer.
喜树碱和VP 16分别被认为是拓扑异构酶I和II的抑制剂。我们以前发现,这些拓扑异构酶抑制剂和蟾蜍灵,一种中药蟾酥的有效成分,诱导各种人类白血病细胞系的分化。本研究旨在探讨这些分化诱导剂诱导人白血病细胞分化的机制。蟾毒灵通过信号转导途径间接抑制HL 60细胞拓扑异构酶II。这些拓扑异构酶抑制剂均可使白血病细胞的细胞周期阻滞于G2/M期。蟾蜍灵与喜树碱或VP 16联合应用对白血病细胞的诱导分化有协同作用。临床上用作急性早幼粒细胞白血病药物的视黄酸与喜树碱或VP 16的组合也显示出对白血病细胞分化的显著协同作用。虽然喜树碱和VP 16是已知的凋亡诱导剂,我们发现蟾毒灵也可以诱导HL 60细胞凋亡时,在更高的浓度比用于诱导分化。喜树碱与VP 16、维甲酸与VP 16、蟾蜍灵与维甲酸联合应用对诱导细胞凋亡有协同作用。这些结果表明,这些拓扑异构酶抑制剂的分化-凋亡诱导治疗癌症的有用性。
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yongkui Jing: "Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differentiation of leukemia HL-60 cells." Leukemia Research. (1994)
景永奎:“拓扑异构酶抑制剂增强了视黄酸对白血病HL-60细胞生长抑制和诱导分化的作用。”
- DOI:
- 发表时间:
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- 影响因子:0
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- 通讯作者:
Yongkui Jing: "Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differenti-ation of leukemia HL-60 cells." Leukemia Research. (1994)
Yongkui Jing:“拓扑异构酶抑制剂增强了视黄酸对白血病HL-60细胞生长抑制和诱导分化的作用。”
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- 发表时间:
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- 影响因子:0
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- 通讯作者:
"The selective inhibitory effect of bufalin on growth of human tumor cells in vitro : Association with the induction of apoptosis in leukemia HL-60 cells." Jpn. J.Cancer Res.85-6 (1994)
“蟾蜍灵对体外人类肿瘤细胞生长的选择性抑制作用:与白血病 HL-60 细胞凋亡的诱导相关。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yongkui Jing: "The selective inhibitory effect of bufalin on growth of human tumor cells in vitro:Association with the induction of apoptosis." Jpn.J.Cancer Res.85. (1994)
景永奎:“蟾蜍灵对体外人肿瘤细胞生长的选择性抑制作用:与诱导细胞凋亡的相关性。”
- DOI:
- 发表时间:
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- 影响因子:0
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Yongkui Jing, Sachiko Hashimoto, Shigeo Nakajo and Kazuyasu Nakaya: "Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth ingibition and induction of differentiation of leukemia HL-60 cells." Leukemia Res.in press. (1994)
Yongkui Jing、Sachiko Hashimoto、Shigeo Nakajo 和 Kazuyasu Nakaya:“拓扑异构酶抑制剂增强了视黄酸对白血病 HL-60 细胞生长激发和诱导分化的作用。”
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NAKAYA Kazuyasu其他文献
NAKAYA Kazuyasu的其他文献
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{{ truncateString('NAKAYA Kazuyasu', 18)}}的其他基金
High resolution analysis of proteins associated with the induction of cell death and carcinogenesis of tumor cells development of chemopreventive agents
与诱导细胞死亡和肿瘤细胞致癌相关的蛋白质的高分辨率分析 化学预防剂的开发
- 批准号:
15590068 - 财政年份:2003
- 资助金额:
$ 1.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of a novel anti-cancer agent from a novel tyrosine kinase inhibitor
从新型酪氨酸激酶抑制剂开发新型抗癌剂
- 批准号:
13672297 - 财政年份:2001
- 资助金额:
$ 1.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies on apoptosis-inducers targeted for the molecules associated with the induction of apoptosis in cancer cells
针对癌细胞凋亡诱导相关分子的凋亡诱导剂研究
- 批准号:
11672182 - 财政年份:1999
- 资助金额:
$ 1.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Effects of isoprenoid compounds on human solid cancer cells
类异戊二烯化合物对人实体癌细胞的影响
- 批准号:
09672251 - 财政年份:1997
- 资助金额:
$ 1.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Combined effects of differentiation-apoptosis inducers on mice inoculated with human leukemia cells.
分化-凋亡诱导剂对接种人白血病细胞的小鼠的综合作用。
- 批准号:
06672239 - 财政年份:1994
- 资助金额:
$ 1.34万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Research on a peptide differentiation factor for myeloid leukemia cells
髓系白血病细胞肽分化因子的研究
- 批准号:
60571058 - 财政年份:1985
- 资助金额:
$ 1.34万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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