Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic effects of 5-FU.

Ryuichi Kawashima, Minoru Haisa, Masashi Kimura, Munenori Takaoka, Yasuhiro Shirakawa, Haruo Takeda, Hirokazu Uetsuka, Mehmet Gunduz, Noriyuki Nagai, Noriaki Tanaka, Yoshio Naomoto

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Abstract

We investigated the role of cyclin A in the cytotoxic effect of 5-fluorouracil (5-FU) on cancer cell lines. Experiments were performed using gastric cancer chemosensitive NUGC3, and chemoresistant NUGC3/5FU/L established by repeated exposure to 5-FU. 5-FU inhibited cell growth of NUGC3 in a dose-dependent manner. Low concentrations of 5-FU did not inhibit cell growth of NUGC3/5FU/L, while high concentrations slightly inhibited cell growth. Examination of the cell cycle pattern of NUGC3 cells showed accumulation at S-phase at 10 micro M and at G1-S-phase at 100 micro M of 5-FU. Cell cycle pattern of NUGC3/5FU/L cells did not change 5-FU concentrations. 5-FU increased cyclin A mRNA level in NUGC3 cells but not NUGC3/5FU/L cells. In the presence of 100 micro M 5-FU, cyclin A protein level increased 2.6-fold in NUGC3 and 1.47-fold in NUGC3/5FU/L. 5-FU dose-dependently increased the percentage of cyclin A-positive NUGC3 cells, but not NUGC3/5FU/L cells. The percentage of cyclin A-positive cells in other 5-FU sensitive esophageal, colon and gastric cancer cell lines (T.Tn, LOVO, DLD-1, MKN-7), increased in the presence of 1 and 10 micro M 5-FU, while cyclin A-positive cells in 5-FU resitant hepatocellular and colon carcinoma cell lines (HCC50 and C-1), did not increase with the same treatment. Our results indicate that the cytotoxic effects of 5-FU in human cancer cell lines correlate with cyclin A and it may be used as a predictive factor for chemotherapy response.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalInternational Journal of Oncology
Volume24
Issue number2
Publication statusPublished - Feb 2004

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Cyclin A
Fluorouracil
Neoplasms
Cell Line
S Phase
Stomach Neoplasms
Cell Cycle
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kawashima, R., Haisa, M., Kimura, M., Takaoka, M., Shirakawa, Y., Takeda, H., ... Naomoto, Y. (2004). Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic effects of 5-FU. International Journal of Oncology, 24(2), 273-278.

Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic effects of 5-FU. / Kawashima, Ryuichi; Haisa, Minoru; Kimura, Masashi; Takaoka, Munenori; Shirakawa, Yasuhiro; Takeda, Haruo; Uetsuka, Hirokazu; Gunduz, Mehmet; Nagai, Noriyuki; Tanaka, Noriaki; Naomoto, Yoshio.

In: International Journal of Oncology, Vol. 24, No. 2, 02.2004, p. 273-278.

Research output: Contribution to journalArticle

Kawashima, R, Haisa, M, Kimura, M, Takaoka, M, Shirakawa, Y, Takeda, H, Uetsuka, H, Gunduz, M, Nagai, N, Tanaka, N & Naomoto, Y 2004, 'Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic effects of 5-FU.', International Journal of Oncology, vol. 24, no. 2, pp. 273-278.
Kawashima, Ryuichi ; Haisa, Minoru ; Kimura, Masashi ; Takaoka, Munenori ; Shirakawa, Yasuhiro ; Takeda, Haruo ; Uetsuka, Hirokazu ; Gunduz, Mehmet ; Nagai, Noriyuki ; Tanaka, Noriaki ; Naomoto, Yoshio. / Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic effects of 5-FU. In: International Journal of Oncology. 2004 ; Vol. 24, No. 2. pp. 273-278.
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abstract = "We investigated the role of cyclin A in the cytotoxic effect of 5-fluorouracil (5-FU) on cancer cell lines. Experiments were performed using gastric cancer chemosensitive NUGC3, and chemoresistant NUGC3/5FU/L established by repeated exposure to 5-FU. 5-FU inhibited cell growth of NUGC3 in a dose-dependent manner. Low concentrations of 5-FU did not inhibit cell growth of NUGC3/5FU/L, while high concentrations slightly inhibited cell growth. Examination of the cell cycle pattern of NUGC3 cells showed accumulation at S-phase at 10 micro M and at G1-S-phase at 100 micro M of 5-FU. Cell cycle pattern of NUGC3/5FU/L cells did not change 5-FU concentrations. 5-FU increased cyclin A mRNA level in NUGC3 cells but not NUGC3/5FU/L cells. In the presence of 100 micro M 5-FU, cyclin A protein level increased 2.6-fold in NUGC3 and 1.47-fold in NUGC3/5FU/L. 5-FU dose-dependently increased the percentage of cyclin A-positive NUGC3 cells, but not NUGC3/5FU/L cells. The percentage of cyclin A-positive cells in other 5-FU sensitive esophageal, colon and gastric cancer cell lines (T.Tn, LOVO, DLD-1, MKN-7), increased in the presence of 1 and 10 micro M 5-FU, while cyclin A-positive cells in 5-FU resitant hepatocellular and colon carcinoma cell lines (HCC50 and C-1), did not increase with the same treatment. Our results indicate that the cytotoxic effects of 5-FU in human cancer cell lines correlate with cyclin A and it may be used as a predictive factor for chemotherapy response.",
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AU - Shirakawa, Yasuhiro

AU - Takeda, Haruo

AU - Uetsuka, Hirokazu

AU - Gunduz, Mehmet

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AU - Naomoto, Yoshio

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