A novel small molecule with potent anticancer activity inhibits cell growth by modulating intracellular labile zinc homeostasis

被引：27

作者：

Huesca, Mario ^{[1
]}

Lock, Lisa S. ^{[1
]}

Khine, Aye Aye ^{[1
]}

Viau, Stephane ^{[1
]}

Peralta, Robert ^{[1
]}

Cukier, I. Howard ^{[1
]}

Jin, Hongnan ^{[1
]}

Al-Qawasmeh, Raed A. ^{[1
]}

Lee, Yoon ^{[1
]}

Wright, Jim ^{[1
]}

Young, Aiping ^{[1
]}

机构：

[1] Lorus Therapeut Inc, Toronto, ON M9W 4Z7, Canada

来源：

MOLECULAR CANCER THERAPEUTICS | 2009年 / 8卷 / 09期

关键词：

KRUPPEL-LIKE FACTOR; DECARBOXYLASE GENE-EXPRESSION; TRANSCRIPTION FACTOR KLF4; INTESTINAL TUMORIGENESIS; PANCREATIC-CANCER; FLUORESCENT-PROBE; DOWN-REGULATION; METAL-IONS; LINE RKO; DIFFERENTIATION;

D O I：

10.1158/1535-7163.MCT-08-1104

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

ML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Kruppel-like factor 4 transcription factor. Kruppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D 1 and promoting the G(1)-S phase arrest of cell proliferation. The antiproliferative and antitumor activity of ML-133 described in the present study suggests modulation of intracellular zinc homeostasis as a potential strategy for the treatment of several cancer types, and ML-133 represents a promising new class of antitumor agents that deserves further development. [Mol Cancer Ther 2009;8(9):2586-96]

引用

页码：2586 / 2596

页数：11

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Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elements [J].