title: 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.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kawashima
authors.forename: Minoru
authors.initials: M
authors.lastname: Haisa
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.forename: Munenori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shirakawa
authors.forename: Haruo
authors.initials: H
authors.lastname: Takeda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uetsuka
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gunduz
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagai
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy; D004396:Coloring Agents / Q000494:pharmacology; D019925:Cyclin A / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000188:drug therapy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D004396:Coloring Agents; D019925:Cyclin A; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D003094:Collagen; C022616:thiazolyl blue; D005472:Fluorouracil