Effects of 5-fluorouracil in nuclear and cellular morphology, proliferation, cell cycle, apoptosis, cytoskeletal and caveolar distribution in primary cultures of smooth muscle cells

• Published in: PloS one Vol. 8; no. 4; p. e63177
• Main Authors: Filgueiras, Marcelo de Carvalho, Morrot, Alexandre, Soares, Pedro Marcos Gomes, Costa, Manoel Luis, Mermelstein, Cláudia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.04.2013; Public Library of Science (PLoS)
• Subjects: 5-Fluorouracil; Actin; Animals; Antimetabolites, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Biology; Biomarkers - metabolism; Cancer; Caveolae - metabolism; Caveolin; Caveolin 3 - metabolism; Cell culture; Cell cycle; Cell Cycle - drug effects; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Chemotherapy; Chick Embryo; Cloning; Colon; Colon cancer; Colorectal cancer; Cytology; Cytoskeleton; Cytoskeleton - metabolism; Deoxyribonucleic acid; DNA; Embryos; Fibers; Fibroblasts; Fluorouracil - pharmacology; G1 phase; Gizzard; Histone H3; Immunoglobulins; Medicine; Morphology; Motility; Muscle contraction; Muscles; Musculoskeletal system; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Organs; Patients; Side effects; Smooth muscle; Tissues; Brazil; United States > US; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063177

Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. The anti-metabolite 5- fluorouracil (5-FU) is widely used in the treatment of patients with colon cancer and other cancer types. 5-FU-based chemotherapy has been shown to be very efficient in the improvement of overall survival of the patients and for the eradication of the disease. Unfortunately, common side effects of 5-FU include severe alterations in the motility of the gastrointestinal tissues. Nevertheless, the molecular and cellular effects of 5-FU in smooth muscle cells are poorly understood. Primary smooth muscle cell cultures are an important tool for studies of the biological consequences of 5-FU at the cellular level. The avian gizzard is one of the most robust organs of smooth muscle cells. Here we studied the molecular and cellular effects of the chemotherapic drug 5-FU in a primary culture of chick gizzard smooth muscle cells. We found that treatment of smooth muscle cells with 5-FU inhibits cell proliferation by the arrest of cells in the G1 phase of cell cycle and induce apoptosis. 5-FU induced a decrease in the percentage of histone H3-positive cells. Treatment of cells with 5-FU induced changes in cellular and nuclear morphology, a decrease in the number of stress fibers and a major decrease in the number of caveolin-3 positive cells. Our results suggest that the disorganization of the actin cytoskeleton and the reduction of caveolin-3 expression could explain the alterations in contractility observed in patients treated with 5-FU. These findings might have an impact in the understanding of the cellular effects of 5-FU in smooth muscle tissues and might help the improvement of new therapeutic protocols for the treatment of colon cancer.