In vivo antitumor activity of DNA-specific ADP-ribosyltransferase, pierisin-1

DNA 特异性 ADP-核糖基转移酶 Pierisin-1 的体内抗肿瘤活性

基本信息

批准号：
15590094
负责人：
WATANABE Masahiko
金额：
$ 2.3万
依托单位：
Shujitsu University (2004)National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590094/
关键词：
cabbage butterfly pierisin ADP-ribosylation in vivo antitumor activity HeLa cells enzyme domain acute toxicity

项目摘要

Pierisin-1, a 98-kDa protein found in cabbage butterfly, exhibits cytotoxicity to cancer cells. To examine whether this protein has anti-cancer activity in viva, acute toxicity to mice and suppression effects to transplanted tumors were analyzed. The LD_<50> value for pierisin-1 was around 5 μg/kg body weight on intraperitoneal injection into BALB/c mice. BALB/c nu/nu female 6-week-old nude mice inoculated 1 x 10^7 HeLa cells on the first day were subjected for intraperitoneal injection of pierisin-1 at a dose of 3 μg/kg on the next day. Thereafter, animals were killed at day 80. Tumors were formed in all ten mice treated without pierisin-1 and the mean tumor weight was 1.16 g per mouse. In mice treated with pierisin-1, the mean tumor weight was 0.56 g per mouse, and its value was significantly lower and no tumors were found in three of ten mice tested. Our results indicate that pierisin-1 has antitumor activity in viva. Next, we purified 47.6 mg pierisin-1 from 1,340 pupae of Pieris rapae. Enzymatic characterization demonstrated that the maximum turnover number of the N-terminal polypeptide and trypsin-treated pierisin-1 were 55 and 25 per second, respectively. Inhibition of the N-terminal enzyme domain by the associated C-terminal fragment was evident under certain conditions. Long-term reactions indicated that a single molecule of pierisin-1 has the capacity to generate more than 10^6 ADP-ribosylated DNA adducts, which could cause the death of a mammalian cell.

Pierisin-1是在白菜蝴蝶中发现的98 kDa蛋白，对癌细胞表现出细胞毒性，以检查蛋白在Viva中的抗癌作用，并分析了抗小鼠的急性毒性。 Pierisin-1的值约为5μg/kg体重，在第一天对BALB/c小鼠的体重为1 x 10^7的Hela细胞。第二天。在十只小鼠中，我们的结果表明，pierisin-1在Viva中具有抗次数活性。每秒55和25，相关的C末端片段的N末端酶结构很明显。哺乳动物细胞。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Matsushima-Hibiya, Y.: "Identification of glycosphingolipid receptors for pierisin-1, a guanine-specific ADP-ribosylating toxin from the cabbage butterfly"J.Biol.Chem.. 278. 9972-9978 (2003)

Matsushima-Hibiya, Y.：“Pierisin-1（一种来自菜蝴蝶的鸟嘌呤特异性 ADP 核糖基化毒素）的糖鞘脂受体的鉴定”J.Biol.Chem.. 278. 9972-9978 (2003)

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Identification of glycosphingolipid receptors for pierisin-1, a guanine-specific ADP-ribosylating toxin from the cabbage butterfly

DOI：
10.1074/jbc.m212114200
发表时间：
2003-03-14
期刊：
JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子：
4.8
作者：
Matsushima-Hibiya, Y;Watanabe, M;Wakabayashi, K
通讯作者：
Wakabayashi, K

Developmental stage-specific expression and tissue distribution of pierisin-1, a guanine-specific ADP-ribosylating toxin, in Pieris rapae

DOI：
10.1016/j.cbpb.2004.07.010
发表时间：
2004-10-01
期刊：
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
影响因子：
2.3
作者：
Watanabe, M;Nakano, T;Wakabayashi, K
通讯作者：
Wakabayashi, K

Totsuka, Y.: "Analysis of HPRT and supF mutations caused by pierisin-1, a guanine specific ADP-ribosylating toxin derived from the cabbage butterfly"Chem.Res.Toxicol.. 16. 945-952 (2003)

Totsuka，Y.：“Pierisin-1（一种源自菜粉蝶的鸟嘌呤特异性 ADP 核糖基化毒素）引起的 HPRT 和 suF 突变的分析”Chem.Res.Toxicol.. 16. 945-952 (2003)