tautomycetin and Colorectal-Neoplasms

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 p21Cip/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 p21Cip/WAF by 150 nmol tautomycetin. The crucial role of p21Cip/WAF1 in the extracellular signal-regulated kinase pathway-dependent antiproliferative responses by tautomycetin was confirmed by using p21Cip/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.

Topics: Animals; Cell Nucleus; Chlorocebus aethiops; Colorectal Neoplasms; COS Cells; Cyclin-Dependent Kinase Inhibitor p21; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Furans; G1 Phase; HCT116 Cells; HeLa Cells; HT29 Cells; Humans; Lipids; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Mice; NIH 3T3 Cells; Phosphoprotein Phosphatases; Proto-Oncogene Proteins c-raf; S Phase