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

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.

• Authors: Ryuichi Kawashima, Minoru Haisa, Masashi Kimura, Munenori Takaoka, Yasuhiro Shirakawa, Haruo Takeda, Hirokazu Uetsuka, Mehmet Gunduz, Noriyuki Nagai, Noriaki Tanaka, Yoshio Naomoto
• Journal: International journal of oncology (Int J Oncol) Vol. 24 Issue 2 Pg. 273-8 (Feb 2004) ISSN: 1019-6439 [Print] Greece
• PMID: 14719102 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Coloring Agents
• Cyclin A
• RNA, Messenger
• Tetrazolium Salts
• Thiazoles
• Collagen
• thiazolyl blue
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Carcinoma, Hepatocellular (drug therapy)
• Cell Line, Tumor
• Collagen (metabolism)
• Colonic Neoplasms (drug therapy)
• Coloring Agents (pharmacology)
• Cyclin A (biosynthesis, metabolism, pharmacology)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Fluorouracil (pharmacology)
• Humans
• Immunoblotting
• Liver Neoplasms (drug therapy)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• S Phase
• Tetrazolium Salts (pharmacology)
• Thiazoles (pharmacology)
• Time Factors