Evaluation of the antitumor activity of 1-(3-C-ethynyl-beta-D-ribofuranosyl) (PJ272), a recent ribonucleoside analogue.
The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C-ethynyl-beta-D-ribofuranosyl)uracil (PJ 272) that we synthesized a few years ago, were investigated in vitro on a variety of tumor cell lines from human and murine origins and in vivo, in tumor bearing mice. Using the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of this compound to depress, at nanomolar concentrations, the growth of leukemia and lymphoma cultured cells. In 7 out of 8 tumor cell lines tested concentration of 50% inhibition (IC50) was found to be less than 25 nM. PJ 272 was also shown to present the same cytotoxicity against K562 Adriamycin-resistant cell line, which express a multi-drug resistance (MDR) phenotype, and its Adriamycin-sensitive parent cell line. Moreover, when injected intraperitoneally at 20 mg/kg every three days, PJ 272 was found to significantly increase the survival rate (T/C = 149%) of DBA/2 mice injected intraperitoneally with L1210 leukemic cells. Taken together, these results suggest that PJ 272 could be considered as a potentially very active drug against lymphoma and leukemia.
Laboratoire de Cancérologie Expérimentale et de Radiobiologie (LCER), Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France.
V
V
Holl
P
P
Jung
D
D
Weltin
J
J
Dauvergne
A
A
Burger
D
D
Coelho
P
P
Dufour
A M
AM
Aubertin
P L
PL
Bischoff
J F
JF
Biellmann
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D005069:Evaluation Studies as Topic; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D020014:K562 Cells; D007939:Leukemia L1210 / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D012263:Ribonucleosides / Q000494:pharmacology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
C103085:1-(3-C-ethynylribopentofuranosyl)uracil; D000970:Antineoplastic Agents; D012263:Ribonucleosides; D014529:Uridine