Search for novel anti-tumor drugs and study on the action mechanism

新型抗肿瘤药物的寻找及作用机制研究

• 批准号: 16590105
• 负责人: HOSAKA Kohei
• 金额: $ 2.3万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590105/
• 关键词: cellular slime mold; differentiation-inducing factor; DIF-1; DIF-1 like factors; leukemia cells; growth inhibitory activity; pharmacological specific target; Dictyopyrones; DIF様因子; 増殖抑制; Dictiostelium mucoroides; 4-methyl-5-n-propylbenzene-1,3-

The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces stalk cell differentiation in the cellular slime mold Dctyostelium discoideum. On the other hand, it has been shown that DIF-1 exhibits anti-tumor activities, inhibition of cell growth (G1 arrest) and induction of cell differentiation or cell differentiation, and induction of apotosis, depending on the concentration of the drug. But the precise signaling system of DIF-1, including the target molecule(s), has been unknown.The results obtained in this project were as follows :i) DIF-1-induced growth arrest of K562 leukemia cells involved the reduction of ERK 1/2 activity.ii) Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) was a pharmacological specific target of DIF-1.iii) Dictyopyrones, novel α-pyronoids isolated from Dctyostelium spp., promoted stalk cell differentiation in Dctyostelium discoideum.iv) A new aromatic compound, brefelamide(4-methyl-5-n-propylbenzene-1,3-diol), from Dicyostelium cellular slime molds showed the inhibitory effect on the proliferation of astrocytoma cells.v) New DIF-1 like factors were isolated from mature fruiting bodies of Armillaria tabescens and Laetiporus sulphureus.

分化诱导因子-1（DIF-1）是诱导盘状软骨黏菌柄细胞分化的信号分子。另一方面，DIF-1显示出抗肿瘤活性、抑制细胞生长（G1停滞）和诱导细胞分化或细胞分化以及诱导细胞凋亡，这取决于药物浓度。本研究的主要结果如下：（1）DIF-1诱导K562白血病细胞的生长停滞与ERK 1/2活性的降低有关;（2）钙调素依赖的环核苷酸磷酸二酯酶（PDE 1）是DIF-1的药理学特异性靶点;（3）Dictyopyrones，一种从Dctyosteophylla spp. iv）从Dicyostestelium细胞黏菌中提取的一种新的芳香族化合物Brefelamide（4-methyl-5-n-propylbenzene-1，3-diol）对星形细胞瘤细胞的增殖具有抑制作用。v）从Armillaria tabescens和Laetiporus sulphureus的成熟子实体中分离到新的DIF-1样因子。

项目成果

Isolation and synthesis of a new aromatic compound, brefelamide, from Dictyostelium cellular slime molds and its inhibitory effect on the proliferation of astrocytoma cells

• DOI: 10.1021/jo051352x
• 发表时间: 2005-10-28
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Kikuchi, H;Saito, Y;Oshima, Y
• 通讯作者: Oshima, Y

Structural requirements of Dictyosterium differentiation-inducing Factors for their stalk-cell-inducing activity in Dictyosterium cells and anti-proliferative activity in K562 human leukemic cells.

网基网藻分化诱导因子在网基网藻细胞中的茎细胞诱导活性和在 K562 人白血病细胞中的抗增殖活性的结构要求。

• 发表时间: 2005
• 期刊: Biochmical Pharmacology 70
• 作者: Gokan N;Kikuchi H;Nakamura K;Oshima Y;Hosaka K;Kubohara Y.
• 通讯作者: Kubohara Y.

Dictyopyrones, novel α-pyronoids isolated from Dictyostelium spp., promote stalk cell differentiation in Dictyostelium discoideum.

盘基吡喃酮是从盘基网柄菌属中分离出来的新型 α-吡喃酮类化合物，可促进盘基网柄菌中的茎细胞分化。

• 发表时间: 2005
• 期刊: Differentiation 73
• 作者: Haruhisa Kikuchi;Arai Akiko
• 通讯作者: Arai Akiko

Prespore-to-stalk convertion involves the production of a pathway-specific glycoprotein, wst25, in the cellular slime mould Dictyosterium discoideum.

前孢子到茎的转化涉及细胞粘菌盘基网藻中途径特异性糖蛋白 wst25 的产生。

• 发表时间: 2004
• 期刊: Biochem.Biophys.Res.Commun. 320
• 作者: Kubohara Y;Arai A;Takahashi K;Hosaka K;Okamoto K
• 通讯作者: Okamoto K

Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is a pharmacological target of differentiation-inducing factor-1, an antitumor agent isolated from Dictyostelium

• DOI: 10.1158/0008-5472.can-03-3551
• 发表时间: 2004-04-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Shimizu, K;Murata, T;Kubohara, Y
• 通讯作者: Kubohara, Y