Comparison of 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine with gemcitabine in its antitumor activity.
The antitumor activity of a novel nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D arabinofuranosyl)cytosine (4'-thio-FAC) was compared with that of 2'-deoxy-2',2'-difluorocytidine (gemcitabine). 4'-Thio-FAC showed potent antitumor effects against various solid cancer cell lines in vitro. Also, gemcitabine showed remarkable in vitro antitumor effects, even more potent than 4'-thio-FAC. However, 4'-thio-FAC inhibited tumor growth more strongly than gemcitabine did at the same dose against human cancer cells implanted s.c. in nude mice. In addition, 4'-thio-FAC suppressed the tumor growth by oral administration. The toxicity of 4'-thio-FAC was weaker than that of gemcitabine in nude mice in both consecutive and intermittent administration. Accordingly, clinical usefulness of 4'-thio-FAC is expected.
Miura
S
S
Biochemicals Division, Yamasa Corporation, Choshi, Chiba, Japan. yamasabi@choshinet.or.jp
Yoshimura
Y
Y
Endo
M
M
Satoh
H
H
Machida
H
H
Sasaki
T
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
C114001:1-(2-deoxy-2-fluoro-4-thio-arabinofuranosyl)cytosine; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003561:Cytarabine; D003841:Deoxycytidine; D000093542:Gemcitabine