In vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine.
The in vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine (4'-thio-DMDC), was examined. 4'-Thio-DMDC inhibited the growth of various cell lines established from human solid cancers, particularly the growth of lung and bladder carcinomas and melanomas. 4'-Thio-DMDC exhibited potent antitumor activity against subcutaneously implanted murine sarcoma S-180 and human fibrosarcoma HT-1080 xenografts. It was shown that 4'-thio-DMDC suppressed cell growth by inhibiting cellular DNA synthesis, and phosphorylation of the 5'-position of its deoxyribose by deoxycytidine kinase was needed for its antitumor activity. 4'-Thio-DMDC is a poor substrate for cytidine deaminase, thus it is a promising agent for the treatment of malignant solid tumors because it will not be converted into its inactive uridine form.
Department of Experimental Therapeutics, Kanazawa University, Japan.
S
S
Miura
M
M
Tanaka
Y
Y
Yoshimura
H
H
Satoh
S
S
Sakata
H
H
Machida
A
A
Matsuda
T
T
Sasaki
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013872:Thionucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C104250:4'-thio-2'-deoxy-2'-methylidenecytidine; D000970:Antineoplastic Agents; D013872:Thionucleosides; D003841:Deoxycytidine; D012313:RNA; D003564:Cytidine Deaminase; C056034:2'-deoxy-2'-methylenecytidine