Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in p53 mutant human colon cancer. 2007

K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan.

IFL [irinotecan (CPT-11), 5-fluorouracil (5-FU), and folinic acid] is one of the treatments for metastatic colorectal cancer. We evaluated cytotoxic effects of a sequentially administered a combination of 5-FU with CPT-11 in human p53 mutant colon cancer. Sequential combination of 5-FU and CPT-11 in human colon cancer SW480 cells using a WST-8 colorimetric assay was studied. Cytotoxicity and cell cycle distribution for each drug were evaluated using an apoptosis assay and flow cytometry. Potential mechanisms of sequence-dependent cytotoxic effects were investigated using microarrays. Cytotoxicity of 5-FU (10, 100, 1000 microM) combined with subsequent use of CPT-11 (1 microM) was significantly greater than the reverse sequence of CPT-11 followed by 5-FU (p < 0.05). Following 24 hrs treatment with 5-FU (0.1-100 microM), no significant apoptosis was observed. In contrast, apoptosis was significantly induced after 24 hrs treatment with CPT-11 (1 and 10 microM). Flow cytometric analysis showed no significant difference in cell cycle distribution between different drug concentrations. We demonstrated up-regulation of 85 genes and down-regulation of 21 genes correlating with sequence-dependent cytotoxicities of 5-FU and CPT-11. The superiority of 5-FU-CPT-11 sequence was proven for p53 mutant colon cancer, SW480. Treatment with 5-FU followed by CPT-11 administration may be the optimal sequence for IFL treatment of metastatic colon cancers.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002166 Camptothecin An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. Camptothecine
D002955 Leucovorin The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS. Calcium Leucovorin,Citrovorum Factor,Folinic Acid,N(5)-Formyltetrahydrofolate,5-Formyltetrahydrofolate,5-Formyltetrahydropteroylglutamate,Calcium Folinate,Folinic Acid-SF,Leucovorin, (D)-Isomer,Leucovorin, (DL)-Isomer,Leucovorin, (R)-Isomer,Leucovorin, Calcium (1:1) Salt,Leucovorin, Calcium (1:1) Salt, (DL)-Isomer,Leucovorin, Calcium (1:1) Salt, Pentahydrate,Leucovorin, Monosodium Salt,Leukovorin,Leukovorum,Wellcovorin,5 Formyltetrahydrofolate,5 Formyltetrahydropteroylglutamate,Acid, Folinic,Factor, Citrovorum,Folinate, Calcium,Folinic Acid SF,Leucovorin, Calcium,Monosodium Salt Leucovorin
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005472 Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid. 5-FU,5-FU Lederle,5-FU Medac,5-Fluorouracil,5-Fluorouracil-Biosyn,5-HU Hexal,5FU,Adrucil,Carac,Efudex,Efudix,Fluoro-Uracile ICN,Fluoroplex,Fluorouracil Mononitrate,Fluorouracil Monopotassium Salt,Fluorouracil Monosodium Salt,Fluorouracil Potassium Salt,Fluorouracil-GRY,Fluorouracile Dakota,Fluorouracilo Ferrer Far,Fluoruracil,Fluracedyl,Flurodex,Haemato-FU,Neofluor,Onkofluor,Ribofluor,5 FU Lederle,5 FU Medac,5 Fluorouracil,5 Fluorouracil Biosyn,5 HU Hexal,Dakota, Fluorouracile,Fluoro Uracile ICN,Fluorouracil GRY,Haemato FU
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077146 Irinotecan A semisynthetic camptothecin derivative that inhibits DNA TOPOISOMERASE I to prevent nucleic acid synthesis during S PHASE. It is used as an antineoplastic agent for the treatment of COLORECTAL NEOPLASMS and PANCREATIC NEOPLASMS. 7-Ethyl-10-hydroxycamptothecin,CPT 11,CPT-11,Camptosar,Camptothecin-11,Irinotecan Hydrochloride,Irrinotecan,NK012 Compound,SN 38,SN 38 11,SN-38,SN-38-11,7 Ethyl 10 hydroxycamptothecin,CPT11,Camptothecin 11,SN3811
D000971 Antineoplastic Combined Chemotherapy Protocols The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form. Anticancer Drug Combinations,Antineoplastic Agents, Combined,Antineoplastic Chemotherapy Protocols,Antineoplastic Drug Combinations,Cancer Chemotherapy Protocols,Chemotherapy Protocols, Antineoplastic,Drug Combinations, Antineoplastic,Antineoplastic Combined Chemotherapy Regimens,Combined Antineoplastic Agents,Agent, Combined Antineoplastic,Agents, Combined Antineoplastic,Anticancer Drug Combination,Antineoplastic Agent, Combined,Antineoplastic Chemotherapy Protocol,Antineoplastic Drug Combination,Cancer Chemotherapy Protocol,Chemotherapy Protocol, Antineoplastic,Chemotherapy Protocol, Cancer,Chemotherapy Protocols, Cancer,Combinations, Antineoplastic Drug,Combined Antineoplastic Agent,Drug Combination, Anticancer,Drug Combination, Antineoplastic,Drug Combinations, Anticancer,Protocol, Antineoplastic Chemotherapy,Protocol, Cancer Chemotherapy,Protocols, Antineoplastic Chemotherapy,Protocols, Cancer Chemotherapy
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

Related Publications

K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
December 2006, Journal of gastroenterology,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
November 1980, The Journal of clinical investigation,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
January 1986, Journal of the National Cancer Institute,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
May 1980, European journal of cancer,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
February 2019, Biochemical pharmacology,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
December 1999, British journal of cancer,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
January 2000, Oncology research,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
May 1998, Clinical cancer research : an official journal of the American Association for Cancer Research,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
July 1985, Cancer research,
K Tanaka, and Y Inoue, and J Hiro, and S Yoshiyama, and Y Toiyama, and T Eguchi, and C Miki, and M Kusunoki
April 2014, Scientific reports,
Copied contents to your clipboard!