| Effect of UCN-01, a selective inhibitor of protein kinase C, on the cell-cycle distribution of human epidermoid carcinoma, A431 cells. | |
| | |
MedLine Citation:
|
PMID: 7506638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
UCN-01 (7-hydroxy-staurosporine), a selective inhibitor of protein kinase C (PKC), was shown to exhibit antitumor activity in murine and human tumor cell lines in vitro and in vivo. On the other hand, staurosporine, a non-selective protein kinase inhibitor, was not shown to exert antitumor activity in vivo despite its potent antiproliferative activity in vitro. To compare the modes of action of UCN-01 and staurosporine in vitro, the effects of both drugs on the cell cycle progression of human epidermoid carcinoma A431 cells were examined by flow cytometry using propidium iodide (PI) staining. At 50% growth inhibitory concentrations, both UCN-01 and staurosporine induced G1 phase accumulation in the cell cycle. At 80% growth inhibitory concentrations, UCN-01 also induced preferential G1 phase accumulation, but staurosporine mostly induced G2M phase accumulation. Staurosporine also induced higher DNA ploidy when the cells were exposed to the drug for more than one generation time of A431 cells. An analysis of cell kinetics by 5-bromo-2-deoxyuridine incorporation versus DNA content confirmed that the G1 phase block by UCN-01 and the G1 and G2M phase block by staurosporine at the respective doses, as was the case for PI staining. Additionally, DNA synthesis of the cells, which was determined by the uptake of 3H-TdR, was not suppressed at least 8 h after the treatment with UCN-01. These results suggested that UCN-01 could affect the G1 phase of cell cycle in A431 cells in quite different manners from staurosporine. The G1 phase block induced by UCN-01 might be important for the growth inhibitory activity of UCN-01 against A431 cells in vitro and in vivo. |
| | |
Authors:
|
S Akinaga; K Nomura; K Gomi; M Okabe |
Related Documents
:
|
8516308 - Lethality induced by a single site-specific double-strand break in a dispensable yeast ... 7190228 - The use of ficoll gradient centrifugation to obtain synchronously growing l5178y cells. 7592778 - Casein kinase ii is required for cell cycle progression during g1 and g2/m in saccharom... 9300578 - Effects of olomoucine, a selective inhibitor of cyclin-dependent kinases, on cell cycle... 160308 - Initiation of dna replication in chromosomes of chinese hamster ovary cells. 9288228 - Asialo gm1-positive cells in mouse cochlea. |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Cancer chemotherapy and pharmacology Volume: 33 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 1994 |
Date Detail:
|
Created Date: 1994-02-17 Completed Date: 1994-02-17 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: GERMANY |
Other Details:
|
Languages: eng Pagination: 273-80 Citation Subset: IM |
Affiliation:
|
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka-ken, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alkaloids
/
pharmacology* Antineoplastic Agents / pharmacology* Carcinoma, Squamous Cell / genetics, pathology* Cell Cycle / drug effects* DNA, Neoplasm / analysis Humans Protein Kinase C / antagonists & inhibitors* Staining and Labeling Staurosporine Time Factors Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Alkaloids; 0/Antineoplastic Agents; 0/DNA, Neoplasm; 112953-11-4/7-hydroxystaurosporine; 62996-74-1/Staurosporine; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Acquired coronary angiogenesis after myocardial infarction.
Next Document: Interaction of acute ventricular dilatation and d-sotalol during sustained reentrant ventricular tac...