Effect of 5-Fluorouracil on the Cell Growth and Cell Cycle Kinetics of a Mouse Ascites Tumor Growing in Vivo

Lewin, Freddi; Skog, Sven; Tribukait, B.; Ringborg, Ulrik

doi:10.3109/02841868709091751

Cited by 14 publications

(13 citation statements)

References 16 publications

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“…No change was observed in induction or repair of CDDP-induced DNA cross links (5). However, the cell cycle arrest in G 2 , seen after CDDP as single drug, could not be seen when CDDP was combined with 5-FU (3,4).…”

mentioning

confidence: 86%

“…Experimental studies have supported the presence of a synergistic effect when the drugs are combined (2,3). The combination of CDDP and 5-FU to in vivogrowing mouse ascites sarcoma cells (Bp8) causes imbalance in the deoxyribonucleotide pools and elevated rate of replicative DNA synthesis (3,4).…”

mentioning

confidence: 99%

“…CDDP does inhibit the cell cycle progression with accumulation of cells in S and arrest in the G 2 phase (3,4,21). CDDP can inactivate the p34 cdc2 -kinase by suppression of the dephosphorylation of p34 cdc2 necessary for onset of mitosis (19)(20)(21), but CDDP did not influence the amount of wee1 or cyclin B (21).…”

mentioning

confidence: 99%

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Cisplatin-Induced Inhibition of p34^cdc2is Abolished by 5-Fluorouracil

Nylén

Welander

et al. 1998

Acta Oncologica

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confidence: 86%

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confidence: 99%

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Cisplatin-Induced Inhibition of p34^cdc2is Abolished by 5-Fluorouracil

Nylén

Welander

et al. 1998

Acta Oncologica

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“…In some studies, sensitivity of growing cells to 5-FU was observed more or less in all cell cycle stages, 1,2) while other studies have found that 5-FU blocks the cell cycle at the G1 and S phases. 3,4) The mechanisms by which 5-FU modulates cell cycle regulation have not been clarified.…”

mentioning

confidence: 99%

Effect of 5‐Fluorouracil on Cell Cycle Regulatory Proteins in Human Colon Cancer Cell Line

Takeda

Haisa

Naomoto

et al. 1999

Japanese Journal of Cancer Research

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We investigated the effects of 5-fluorouracil (5-FU) on cell cycle-regulating proteins in RPMI 4788 cells. 5-FU inhibited cell growth dose-dependently and this growth inhibition was accompanied with cell cycle accumulation in early S phase and increased expression of cyclin A. When cells were released from short-term treatment (3 or 24 h) with 5-FU, the cell cycle started to progress again and cyclin A protein levels decreased. Cyclin A-associated kinase activity assay showed that cyclin A-cyclin-dependent kinase (Cdk) 2 kinase activity was altered by 5-FU treatment concomitantly with the changes in cell cycle state seen in flow cytometric analysis. Furthermore, the elevation of cyclin A protein level by 5-FU treatment was observed in three other human cancer cell lines, DLD-1, H226Br and T.Tn. These results suggest that cyclin A protein levels in cancer cells are increased by 5-FU, and the cyclin A function and degradation mechanism remain normal.Key words: 5-FU -Cyclin A -Cell cycle -Exposure time 5-Fluorouracil (5-FU) has been used clinically for over 30 years and it exerts its effect on proliferating cells by interfering with DNA synthesis. Many aspects of the cellular and molecular pharmacology of 5-FU have been investigated in vitro, as well as in vivo. In some studies, sensitivity of growing cells to 5-FU was observed more or less in all cell cycle stages, 1, 2) while other studies have found that 5-FU blocks the cell cycle at the G1 and S phases.3, 4) The mechanisms by which 5-FU modulates cell cycle regulation have not been clarified.Recently, considerable progress has been made in identifying proteins whose expression and activity regulate the cell cycle. The progression through the cell cycle is thought to be driven by sequential activation of cyclindependent kinases (Cdks) through binding to specific cyclins. 5-7) Cyclin A is a cell cycle regulating protein that binds to Cdk2 or Cdc2 proteins and plays an important role in regulating the S phase transition. 8)In this paper, we investigated the effect of 5-FU on cell cycle progression from the viewpoint of the cell cycle regulatory proteins, using asynchronous cells. MATERIALS AND METHODSCell culture and experimental group RPMI 4788 cells derived from human colon cancer (supplied by Roswell Park Memorial Institute, Buffalo, NY 9) ) were maintained in RPMI 1640 medium supplemented with 10% fetal calf serum (FCS). Cells were seeded in 75-cm 2 tissue culture bottles at 5×10 5 cells/bottle, and cultured at 37°C in a 5% CO 2 incubator. After 72 h preculture, culture medium was changed to RPMI 1640 medium containing 10% FCS with or without 5-FU (0.1 to 100 µM) for in vitro experiments. 5-FU was purchased from Kyowa Hakko Kogyo Co., Ltd., Tokyo. In the continuous exposure experiment, cells were harvested at the time point of 6, 12, 24 or 48 h for the following experiments. In the short-term exposure experiment, cells were exposed for 3 or 24 h to 5-FU, followed by culture without 5-FU for 24, 48 or 72 h. Viable cells were washed three times with ice-cold pho...

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“…The DNA-histogram changes could be interpreted as DNA synthesis inhibition, but could also be an indication of increased outflow of cells from the G1 phase without DNA synthesis inhibition. Earlier we found that the cell flow from G, to S was elevated after a 5-FU dose of 0.3-0.9mg/animal and that the cell flow through the S-phase, i.e., the DNA synthesis, was just slightly inhibited (22). In this work it had to be increased to 2.7 mg/animal to give any reduction of the DNA synthesis.…”

Section: Acta Oncologicamentioning

confidence: 72%

Absence of Misincorporation of Pyrimidines in DNA After Treatment with a Combination of Cisplatin (CIS-Diammine-Dichloro-Platinum) and 5-Fluorouracil of Mouse Sarcoma Cells

1996

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Effect of 5-Fluorouracil on the Cell Growth and Cell Cycle Kinetics of a Mouse Ascites Tumor Growing in Vivo

Cited by 14 publications

References 16 publications

Cisplatin-Induced Inhibition of p34^cdc2is Abolished by 5-Fluorouracil

Cisplatin-Induced Inhibition of p34^cdc2is Abolished by 5-Fluorouracil

Effect of 5‐Fluorouracil on Cell Cycle Regulatory Proteins in Human Colon Cancer Cell Line

Absence of Misincorporation of Pyrimidines in DNA After Treatment with a Combination of Cisplatin (CIS-Diammine-Dichloro-Platinum) and 5-Fluorouracil of Mouse Sarcoma Cells

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Effect of 5-Fluorouracil on the Cell Growth and Cell Cycle Kinetics of a Mouse Ascites Tumor Growing in Vivo

Cited by 14 publications

References 16 publications

Cisplatin-Induced Inhibition of p34cdc2is Abolished by 5-Fluorouracil

Cisplatin-Induced Inhibition of p34cdc2is Abolished by 5-Fluorouracil

Effect of 5‐Fluorouracil on Cell Cycle Regulatory Proteins in Human Colon Cancer Cell Line

Absence of Misincorporation of Pyrimidines in DNA After Treatment with a Combination of Cisplatin (CIS-Diammine-Dichloro-Platinum) and 5-Fluorouracil of Mouse Sarcoma Cells

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Cisplatin-Induced Inhibition of p34^cdc2is Abolished by 5-Fluorouracil

Cisplatin-Induced Inhibition of p34^cdc2is Abolished by 5-Fluorouracil