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Research Articles: Therapeutics, Targets, and Development

Tautomycetin inhibits growth of colorectal cancer cells through p21^cip/WAF1 induction via the extracellular signal–regulated kinase pathway

¹ National Research Laboratory of Molecular Complex Control, Departments of ² Biotechnology and ³ Biochemistry, Yonsei University, Seoul, Korea and ⁴ For HumanTech Co., Ltd, Kowoon Institute of Technology Innovation, Suwon, Korea

Requests for reprints: Kang-Yell Choi, Department of Biotechnology, Yonsei University, 134 Shinchon-Dong, Seodemun-Gu, Seoul 120-749, Korea. Phone: 82-2-2123-2887; Fax: 82-2-362-7265. E-mail: kychoi{at}yonsei.ac.kr

Abstract

Tautomycetin is an antifungal antibiotic retaining potent immunosuppressive function. We have identified the roles of tautomycetin on cellular proliferation and transformation of colorectal cancer cells. The proliferation and anchorage-independent growth of HCT-15, HT-29, and DLD-1 colorectal cancer cells were efficiently inhibited without induction of apoptosis by 150 nmol tautomycetin. These growth inhibitory effects were dependent on p21^Cip/WAF induction via the extracellular signal–regulated kinase pathway, and the tautomycetin effects were abolished in HCT-116 colon cells and eight other types of cells that did not induce p21^Cip/WAF by 150 nmol tautomycetin. The crucial role of p21^Cip/WAF1 in the extracellular signal–regulated kinase pathway–dependent antiproliferative responses by tautomycetin was confirmed by using p21^Cip/WAF1 gene–deleted HCT-116 cells. The growth inhibitory effect of tautomycetin was acquired by regulation of Raf-1 activity through inhibition of protein phosphatase type 1 and protein phosphatase type 2A with high preference toward protein phosphatase type 1. Tautomycetin could be a potential drug for colorectal cancer. [Mol Cancer Ther 2006;5(12):3222–31]

Grant support: National Research Laboratory (NRL) Grant and Protein Network Research Center from the Korea Ministry of Science and Technology and Korea Health Industry Development Institute from the Korea Ministry of Health and Welfare.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/ 1/06; revised 9/ 4/06; accepted 10/19/06.