Cellular and pharmacological bases of the antitumor activity of a novel adamantyl retinoid, ST1926.
ST1926 is a novel related adamantyl retinoid endowed with potent antiproliferative and apoptogenic activity. The drug induced an early G1/S cell cycle arrest which was associated with a typical DNA damage response including modulation of genes involved in cell cycle regulation and DNA repair. The evidence of the drug ability to induce a significant extent of DNA strand breaks after short-term exposure is consistent with the cellular response. ST1926 is active by oral administration both on hematological and on solid tumors. The more marked antitumor effect showed by ST1926 in immuno-competent mice rather than in tumor xenografts suggests a contribution of indirect host-mediated antitumor effects in addition to a direct antiproliferative activity against tumor cells.
Pisano
C
C
Sigma-Tau, Pomezia (Rome), Italy.
Merlini
L
L
Penco
S
S
Carminati
P
P
Zunino
F
F
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
C472791:3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid; D000970:Antineoplastic Agents; D002934:Cinnamates; D000218:Adamantane