| Differential effects of N-(4-hydroxyphenyl)retinamide and retinoic acid on neuroblastoma cells: apoptosis versus differentiation. | |
| | |
MedLine Citation:
|
PMID: 7850799 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Retinoids exert various important biological effects in the control of normal growth, differentiation, and fetal development. While retinoic acid (RA) has entered clinical trials as a differentiation-promoting agent, it is only recently that the synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) has been shown to be of potential clinical interest in cancer chemoprevention and treatment. Since thus far no data exist on the effects of HPR on neural crest cell-derived tumors, we have examined its in vitro effects on neuroblastoma (NB) cell lines and found that at relevant pharmacological concentrations it induces a dose-dependent growth inhibition. The antiproliferative effects of HPR were, in six of six cell lines tested, drastically more potent that those induced by an equimolar dose of RA. Time course growth analysis showed that HPR at 3 x 10(-6) M induces a very rapid (24-72 h) fall in thymidine uptake (> 90%), whereas at 3 x 10(-7) M it exhibits cytostatic effects. In contrast to RA, HPR did not show morphological changes typical of NB cell maturation nor did it induce the expression of any cytoskeletal protein associated with neuronal differentiation. DNA flow cytofluorimetric analysis revealed that HPR did not induce an arrest in a specific phase of the cell cycle while triggering apoptosis. This phenomenon was evidenced both by the visualization of "DNA ladders" on gel electrophoresis and by a quantitative assay for evaluating programmed cell death based upon the labeling of DNA breaks with tritiated thymidine. With the latter method, apoptotic cells were detectable as early as 3-6 h after treatment of NB cells with 10(-5) M HPR, while more than 50% of cells were apoptotic by 24-72 h following exposure to 3 x 10(-6) M HPR. In contrast, RA induced a low rate of apoptosis in NB cells only after 3-5 days. Time lapse photomicroscopy showed that NB cells treated with HPR underwent a death process highly reminiscent of apoptosis, with progressive condensation of the cytoplasm around the nucleus and intense cell shrinkage. The cells then rounded up and detached from the plate. Furthermore, propidium iodide staining of the DNA showed that a high proportion of cells treated with HPR displayed a small and brightly staining nucleus; chromatin appeared aggregated into dense masses in the nuclear periphery, a typical feature of apoptotic cells. In conclusion, our study demonstrates that contrary to the differentiation-promoting activity of RA, HPR dramatically suppresses NB cell growth by inducing programmed cell death.(ABSTRACT TRUNCATED AT 400 WORDS) |
| | |
Authors:
|
M Ponzoni; P Bocca; V Chiesa; A Decensi; V Pistoia; L Raffaghello; C Rozzo; P G Montaldo |
Related Documents
:
|
1691719 - Insulin and epidermal growth factor stimulate phosphorylation of p185her-2 in the breas... 2998599 - Changes in receptor occupancy and growth factor responsiveness induced by treatment of ... 7729599 - Retinoic acid is a potent growth activator of mouse primordial germ cells in vitro. 8348619 - Epidermal growth factor-induced actin remodeling is regulated by 5-lipoxygenase and cyc... 6582309 - Modulation by retinoic acid of cellular, surface-exposed, and secreted glycoconjugates ... 9662339 - Transition from sclc to nsclc phenotype is accompanied by an increased tre-binding acti... 1602739 - Cysteine proteinase inhibitor in cultured human medullary thyroid carcinoma cells. 15985059 - Circadian variation of the cell proliferation in the jejunal epithelium of rats at wean... 14990389 - Model of the developing tumorigenic phenotype in mammalian cells and the roles of susta... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cancer research Volume: 55 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1995 Feb |
Date Detail:
|
Created Date: 1995-03-14 Completed Date: 1995-03-14 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 853-61 Citation Subset: IM |
Affiliation:
|
Oncology Research Laboratory, G. Gaslini Children's Hospital, Genoa, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Apoptosis
/
drug effects* Cell Cycle / drug effects Cell Differentiation / drug effects Cell Division / drug effects Cytoskeletal Proteins / analysis, drug effects DNA Damage DNA, Neoplasm / analysis, drug effects, metabolism Fenretinide / pharmacology* Fluorescent Antibody Technique Humans Neuroblastoma / drug therapy*, pathology* Neurons / cytology, drug effects Tretinoin / pharmacology* |
| Chemical | |
Reg. No./Substance:
|
0/Cytoskeletal Proteins; 0/DNA, Neoplasm; 302-79-4/Tretinoin; 65646-68-6/Fenretinide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Identification of a point mutation in the folate receptor gene that confers a dominant negative phen...
Next Document: Efficacy of the quinocarmycins KW2152 and DX-52-1 against human melanoma lines growing in culture ka...