Abstract
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.
Highlights
Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. 5- fluorouracil (5-FU) is a commonly used chemotherapy agent in the treatment of human colon cancer [1]
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. 5-FU is a pyrimidine analogue, that within the cell, is converted into 5-fluoro-29deoxy59monophosphate resulting in the inhibition of thymidylate synthase with the subsequent suppression of DNA synthesis [2]
In the present work we studied the effects of the anti-metabolite drug 5- fluorouracil (5-FU) in the overall cellular morphology, cytoskeletal and caveolar organization, cell proliferation and cell death of chick cultured smooth muscle cells
Summary
Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. 5-FU is a commonly used chemotherapy agent in the treatment of human colon cancer [1]. In the present work we studied the effects of the anti-metabolite drug 5- fluorouracil (5-FU) in the overall cellular morphology, cytoskeletal and caveolar organization, cell proliferation and cell death of chick cultured smooth muscle cells. 5-FU induces a decrease in the total cell number in cultures of smooth muscle cells.
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