A novel atypical retinoid endowed with proapoptotic and antitumor activity.
The novel atypical retinoid E-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926, 4) exhibited a potent antiproliferative activity on a large panel of human tumor cells. Despite almost complete loss of ability to activate RARs, the compound was an effective apoptosis inducer and surprisingly produced DNA damage, that likely contributes to the proapoptotic activity. Following oral administration, 4 was well tolerated and caused tumor growth inhibition in the ovarian carcinoma, A2780/DX, and in the human melanoma, MeWo, growing in nude mice, thus supporting the therapeutic interest of the novel agent.
Cincinelli
Raffaella
R
Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Milano, Italy.
Dallavalle
Sabrina
S
Merlini
Lucio
L
Penco
Sergio
S
Pisano
Claudio
C
Carminati
Paolo
P
Giannini
Giuseppe
G
Vesci
Loredana
L
Gaetano
Carlo
C
Illy
Barbara
B
Zuco
Valentina
V
Supino
Rosanna
R
Zunino
Franco
F
D000218:Adamantane / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C472791:3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid; D000970:Antineoplastic Agents; D002934:Cinnamates; D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D000218:Adamantane