Growth inhibition and apoptotic cell death in uterine cervical carcinoma cells induced by 5-fluorouracil
| Autor: | Minoru Ueki, Chiharu Inoki, Ichiro Orino, Masatsugu Ueda, Ken Ueki, Koji Kumagai |
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| Rok vydání: | 1997 |
| Předmět: |
Antimetabolites
Antineoplastic Cancer Research Programmed cell death Pathology medicine.medical_specialty Uterine Cervical Neoplasms Apoptosis DNA Fragmentation Adenocarcinoma Biology Fas ligand Antigens Neoplasm Tumor Cells Cultured Carcinoma medicine Humans fas Receptor TUNEL assay Cell growth Flow Cytometry medicine.disease Molecular biology Oncology Cell culture Carcinoma Squamous Cell DNA fragmentation Female Fluorouracil Cell Division |
| Zdroj: | International Journal of Cancer. 71:668-674 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/(sici)1097-0215(19970516)71:4<668::aid-ijc25>3.0.co;2-6 |
| Popis: | We have investigated the effects of 5-fluorouracil (5-FU) on cell growth, DNA synthesis, morphological changes, DNA fragmentation and Fas antigen expression of cultured human uterine cervical carcinoma cells (OMC-1 squamous-cell carcinoma and OMC-4 adenocarcinoma). Apoptotic cell death in cervical carcinoma tissues from the patients after an intravenous administration of 5-FU was also examined. Treatment of OMC-1 and OMC-4 cells with 0.1–10 μg/ml of 5-FU (1 μg/ml = 7.7 μM) resulted in concentration-dependent inhibition of the number of cumulative viable cells and 6-3H-deoxyuridine uptake into the DNA. These effects of 5-FU were well correlated with apoptotic indices of the cells determined in situ by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end-labeling (TUNEL). A TUNEL signal was detectable in nuclei of normal-looking cells and in a lobulated nucleus with dense chromatin. DNA fragmentation was observed in the cells exposed to 10 μg/ml of 5-FU according to the nucleosomal ladder detected by electrophoresis. Flow cytometric analysis showed that Fas antigen expression of the cells increased upon incubation with 10 μg/ml of 5-FU. Moreover, TUNEL of tissue sections of resected uterus revealed that apoptosis occurred more frequently in patients treated pre-operatively with 500 mg/m2/day of 5-FU for 8 days than in those who did not receive 5-FU. These results suggest that achievable therapeutic levels of 5-FU inhibit cell growth and DNA synthesis and induce apoptotic cell death in uterine cervical carcinoma cells. However, the relationship between 5-FU-mediated apoptosis and the Fas ligand/Fas system remains to be explored. Int. J. Cancer 71:668–674, 1997. © 1997 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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