Document Detail

Inductions of fibroblast-like morphology and high growth activity by low-dose CPT-11 in PC12 cells: role of tenascin.
MedLine Citation:
PMID:  10906440     Owner:  NLM     Status:  MEDLINE    
The chemotherapeutic agent CPT-11 induces apoptotic cell death in various cells. In the present study we examined the effect of CPT-11 in rat pheochromocytoma PC12 cells. When PC12 cells were treated with CPT-11, two distinct reactions were encountered. A high dose of CPT-11 induced apoptotic cell death mediated by caspase cascade, whereas a low dose of CPT-11 induced irreversible cell morphological changes. The cell shape of the transformed PC12 cells was similar to fibroblasts, and these were termed FLTP12 (fibroblast-like transformed PC12). FLTP12 cells showed some differences from the original PC12 cells. In addition, cultured media of passed FLTP12 cells induced same cell transformation in PC12 cells. To examine how this transformation may be triggered, the possible involvement of a growth factor(s) was investigated. Among those tested, the possible involvement of basic fibroblast growth factor (basic-FGF) was observed, whereas basic FGF antibody did not affect the induction of cell transformation. Molecular sieve analysis revealed that transformation-inducing factor is large molecule protein like cell attachment factors (>100K), and we demonstrated the direct involvement of tenascin in the transformation of PC12 cell.
A Suzuki; Y Tsutomi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  14     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-08-17     Completed Date:  2000-08-17     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  337-43     Citation Subset:  IM    
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd, Tokyo R&D Center 16-13, Kitakasai 1, Edogawa-ku, 134, Tokyo, Japan.
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MeSH Terms
Antineoplastic Agents, Phytogenic / toxicity*
Apoptosis / drug effects
Camptothecin / analogs & derivatives*,  toxicity
Carboxylic Acids / pharmacology
Caspases / antagonists & inhibitors,  metabolism
Cell Division / drug effects,  physiology
Cell Nucleus / drug effects,  pathology
Cell Survival / drug effects
Cell Transformation, Neoplastic / drug effects
Culture Media, Conditioned / pharmacology
DNA Fragmentation
Dactinomycin / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Fibroblasts / cytology,  drug effects*,  physiology
Oligopeptides / pharmacology
PC12 Cells / cytology,  drug effects*,  physiology
Tenascin / physiology*
Tumor Necrosis Factor-alpha / pharmacology
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Carboxylic Acids; 0/Culture Media, Conditioned; 0/Enzyme Inhibitors; 0/Fumonisins; 0/Oligopeptides; 0/Tenascin; 0/Tumor Necrosis Factor-alpha; 0/aspartyl-glutamyl-valyl-aspartal; 100286-90-6/irinotecan; 116355-83-0/fumonisin B1; 143313-51-3/L 709049; 50-76-0/Dactinomycin; 7689-03-4/Camptothecin; EC 3.4.22.-/Caspases

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