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
• 负责人: NAKAYA Kazuyasu
• 金额: $ 1.34万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672239/
• 关键词: leukemia; differentiation; apoptosis; combined effect; apoptosis-inducer; differentiation-inducer

We have found that geranylgeraniol (GGO) is a potent inducer of apoptosis in various tumor cell lines including human myeloid leukemia, lymphoblastic, and adenocarcinoma. Upon treatment of HL-60 cells with 50 muM GGO, 85% of DNA was fragmented in 3 h. [^3H] GGO was taken up by HL-60 cells in 3 h and was incorporated into several proteins with molecular masses from 10.5 to 20.1 kDa, suggesting these proteins were geranylgeranylated. The expression of c-myc and bc1-2 decreased significantly within 3 h.To explore agents for differentiation-apoptosis therapy of leukemia, various combinations of differentiation-and apoptosis-inducers were examined for the strongest apoptosis-inducing activity for human HL-60 cells. The strongest apotosis-inducing acitvity on HL-60 cells were obtained by combining with retinoic acid, bufalin, and VP16. Administration of the combination of retinoic acid, bufalin, and VP16 to mice inoculated with HL-60 cells was makedly effective in prolongation of survival.

我们发现香叶香叶醇（GGO）是多种肿瘤细胞系（包括人髓性白血病、淋巴细胞和腺癌）的有效诱导细胞凋亡剂。用50 muM GGO处理HL-60细胞后，3 h内85%的DNA片段化。[^3H] GGO在3 h内被HL-60细胞吸收，并结合到分子质量在10.5 - 20.1 kDa之间的几个蛋白中，表明这些蛋白是香叶酰化的。c-myc和bc1-2的表达在3 h内显著降低，为了探索白血病的分化-凋亡治疗药物，我们检测了不同的分化和凋亡诱导剂组合对人HL-60细胞的最强凋亡诱导活性。与维甲酸、蟾毒灵和VP16联合使用对HL-60细胞的诱导凋亡活性最强。将视黄酸、蟾毒灵和VP16联合应用于HL-60细胞接种的小鼠，可有效延长存活时间。

项目成果

Hidekazu OHIZUMI: "Geranylgeraniol is a potent inducer of apoptosis in tumor cells." J. Biochem.117. 11-13 (1995)

Hidekazu OHIZUMI：“香叶基香叶醇是肿瘤细胞凋亡的有效诱导剂。”

Itaru SAKAI: "Novel role vitmin K2 : a potent inducer of differentiaionof various human myeloid leukemia cell lines" Biochem. Biophys. Res. Commun.205. 1305-1310 (1994)

Itaru SAKAI：“维生素 K2 的新作用：多种人类骨髓性白血病细胞系分化的有效诱导剂”Biochem。

Hidekazu OHIZUMI: "Geranylgeraniol is a potent inducer of apoptosis in tumor cells." J.Biochem.117. 11-13 (1995)

Hidekazu OHIZUMI：“香叶基香叶醇是肿瘤细胞凋亡的有效诱导剂。”

Itaru Sakai, Schiko Hashimoto, Madoka Yoda, Takayuki Hida, Shigemitsu Osawa, Shigeo Nakajo and kazuyasu Nakaya: "Role of vitamin K2 ; a potent inducer of differentiation of various human myeloid leukemia cell lines" Biochem.Biophys.Res.Commun.205. 1305-13

Itaru Sakai、Schiko Hashimoto、Madoka Yoda、Takayuki Hida、Shigemitsu Osawa、Shigeo Nakajo 和 kazuyasu Nakaya：“维生素 K2 的作用；各种人类骨髓性白血病细胞系分化的有效诱导剂”Biochem.Biophys.Res.Commun.205。

Itaru SAKAI: "Novel role of vitamin K2:a potent inducer of differentiaionof various human myeloid leukemia cell lines." Biochem.Biophys.Res.Commun.205. 1305-1310 (1994)

Itaru SAKAI：“维生素 K2 的新作用：多种人类骨髓性白血病细胞系分化的有效诱导剂。”