Effect of 5-fluorouracil on G1 phase cell cycle regulation in oral cancer cell lines

• Published in: Oral oncology Vol. 40; no. 1; pp. 63 - 70
• Main Authors: Li, Ming-Heng, Ito, Daisuke, Sanada, Misaki, Odani, Takeshi, Hatori, Masashi, Iwase, Masayasu, Nagumo, Masao
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2004; Elsevier
• Subjects: 5-FU; Antimetabolites, Antineoplastic - pharmacology; Antineoplastic Agents - pharmacology; Biological and medical sciences; Blotting, Western; CDK inhibitors (CKIs); Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cisplatin - pharmacology; Cyclin; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-dependent kinases (CDKs); Cyclins - metabolism; DNA, Neoplasm - metabolism; Fluorouracil - pharmacology; G1 Phase - drug effects; Humans; Medical sciences; Mouth Neoplasms - drug therapy; Otorhinolaryngology. Stomatology; Reverse Transcriptase Polymerase Chain Reaction - methods; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - metabolism; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Cyclin; Cyclin-dependent kinases (CDKs); CDK inhibitors (CKIs); 5-FU; Antineoplastic agent; Oral cancer; Regulation(control); Cancerology; Cell cycle; Tumor cell; Fluorouracil; Enzyme; Stomatology; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; Biological activity; G1 Phase; Cell line; Antimetabolic; Methyltransferases; Kinase; Pyrimidine derivatives; Oral cavity disease
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/S1368-8375(03)00136-2

5-Fluorouracil (5-FU) has been widely used for chemotherapy of head and neck cancer, and is known to affect the cell cycle and induce apoptotic death of cancer cells. However, the molecular actions of 5-FU on the cell cycle regulatory mechanism have not been fully explained. Herein we analyzed the effects of 5-FU on the expression of G1/S-related cell cycle regulators in oral cancer cell lines. In vitro 5-FU treatment of oral cancer cells resulted in an increase in G1/S phase cells. p21 expression was augmented by 5-FU without any notable changes in p53 expression. A remarkable up-regulation of cyclin E and a concomitant down-regulation of cyclin D were observed after 24 h 5-FU treatment. Our results suggest that 5-FU-induced changes in cell cycle regulation of oral cancer cells might associate with an alteration of G1 cyclins expression. p21 was remarkably up-regulated, but it was speculated that its activity might be cancelled by an increased binding to CDK4.