Document Detail


The novel atypical retinoid ST1926 is active in ATRA resistant neuroblastoma cells acting by a different mechanism.
MedLine Citation:
PMID:  17150196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
E-3-(4'-Hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) is a novel orally available compound belonging to the class of synthetic atypical retinoids. These agents are attracting growing attention because of their unique mechanism of antitumor action that appears different from that of classical retinoic acid. This study aims at investigating the antitumor activity of ST1926 in neuroblastoma (NB) preclinical models. In vitro, ST1926 was more cytotoxic than both its prototype, CD437 and all-trans-retinoic acid (ATRA) and it was active in the SK-N-AS cell line, which is refractory to ATRA. We showed that unlike ATRA, ST1926 does not induce morphological differentiation in NB cells where it produces indirect DNA damage, cell cycle arrest in late S-G2 phases and p53-independent programmed cell death. DNA damage was not mediated by oxidative stress and was repaired by 24h after drug removal. The SK-N-DZ cell line appeared the most sensitive to the proapoptotic activity of ST1926, probably because both the extrinsic and intrinsic pathways appear involved in the process. Studies with Z-VAD-FMK, suggested that ST1926 might also mediate caspase-independent apoptosis in NB cells. In vivo, orally administered ST1926, appeared to inhibit tumor growth of NB xenografts with tolerable toxicity. Overall, our results support the view that ST1926 might represent a good drug candidate in this pediatric tumor.
Authors:
Angela Maria Di Francesco; Daniela Meco; Anna Rita Torella; Giuseppe Barone; Maurizio D'Incalci; Claudio Pisano; Paolo Carminati; Riccardo Riccardi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-07
Journal Detail:
Title:  Biochemical pharmacology     Volume:  73     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-02     Completed Date:  2007-03-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  643-55     Citation Subset:  IM    
Affiliation:
Division of Pediatric Oncology, Catholic University of Rome, Largo A Gemelli 8, 00168 Rome, Italy. labfarm2@rm.unicatt.it
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MeSH Terms
Descriptor/Qualifier:
Adamantane / administration & dosage,  analogs & derivatives*,  chemistry,  pharmacology
Animals
Antineoplastic Agents / administration & dosage,  chemistry,  pharmacology*
Cell Cycle / drug effects
Cell Line, Tumor
Cinnamates / administration & dosage,  chemistry,  pharmacology*
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Resistance, Neoplasm*
Humans
Male
Mice
Mice, Nude
Molecular Structure
Neuroblastoma / drug therapy*,  pathology*
Tretinoin / pharmacology*
Chemical
Reg. No./Substance:
0/3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid; 0/Antineoplastic Agents; 0/Cinnamates; 281-23-2/Adamantane; 302-79-4/Tretinoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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