title: In vitro antitumor activity of TAS-103 against freshly-isolated human colorectal cancer.
abstract: DNA topoisomerases (Topo) are enzymes that relieve the secondary twist on the DNA strand in the process of DNA synthesis and transcription; therefore they are unique targeting molecules for the chemotherapy of colorectal cancer. TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-in-deno [2,1-c]quinolin-7-one dihydrochloride, MW; 406.31), a novel quinoline derivative, has recently been established as a Topo I and Topo II inhibitor. The aim of the present study was to investigate the antitumor activity of TAS-103 by the MTT assay in human highly-purified and freshly-isolated colorectal cancer cells. To our knowledge, this is the first data concerning the antitumor activity of TAS-103 in highly-purified and isolated human colorectal cancer cells. TAS-103 showed the strongest antitumor activity among the conventional anticancer agents for colorectal cancer (p<0.05). The combination with CDDP augmented the antitumor activity of TAS-103 (p<0.05), indicating that CDDP is one of the most potent candidates to be used in combination with TAS-103. To predict the clinical effect of TAS-103, the expressions of Topo I and Topo II were measured by quantitative PCR. However, a correlation between the expression of Topo and the antitumor activity of TAS-103 was not established. In conclusion, according to this data, TAS-103 may be useful in the chemotherapy of colorectal cancer.
authors.affiliation: Department of Surgery and Bioengineering, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Japan. tsunodat@ims.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Tsunoda
authors.forename: H
authors.initials: H
authors.lastname: Tanimura
authors.forename: H
authors.initials: H
authors.lastname: Yamaue
authors.forename: K
authors.initials: K
authors.lastname: Ishimoto
authors.forename: T
authors.initials: T
authors.lastname: Kobunai
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007192:Indenes / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013778:Tetrazolium Salts; D013844:Thiazoles; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007192:Indenes; D013778:Tetrazolium Salts; D013844:Thiazoles; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; C022616:thiazolyl blue; D002945:Cisplatin; C106647:6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one