Document Detail


Sansalvamide induces pancreatic cancer growth arrest through changes in the cell cycle.
MedLine Citation:
PMID:  20150619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Survival of patients with pancreatic cancer remains poor due to inadequate chemotherapeutic options. Sansalvamide A, a cyclic depsipeptide produced by a marine fungus, has demonstrated significant anticancer activity. We previously observed antiproliferative effects in a series of sansalvamide A analogs in pancreatic cancer cells, one of which was further evaluated in this study. Two human pancreatic cancer cell lines (AsPC-1 and CD18) were incubated with increasing concentrations (10-50 muM) of the sansalvamide analog. Cell proliferation was then measured by thymidine incorporation and cell counting, and cell cycle analysis was determined by flow cytometry. Western blot analysis was used to evaluate expression of cyclin D1, cdk4, cdk6, cyclin E, cyclin A, cdk2, and p21. Sansalvamide caused G(1) phase cell cycle arrest in both cell lines, and Western blot analyses demonstrated up-regulation of p21, down-regulation of cyclins D1, E, and A, and cdk4, consistent with G(0)/G(1) cell cycle arrest. Cumulatively the results show that Sansalvamide A attenuates pancreatic cancer cell growth and represents a potential anticancer therapy.
Authors:
Michael J Heiferman; Mohammad R Salabat; Michael B Ujiki; Matthew J Strouch; Eric C Cheon; Richard B Silverman; David J Bentrem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-12     Completed Date:  2010-03-17     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  73-8     Citation Subset:  IM    
Affiliation:
Department of Surgery, Feinberg School of Medicine, Northwestern University, Suite 650, 676 N Saint Clair, Chicago, IL 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / drug effects
Cell Growth Processes / drug effects
Cell Line, Tumor
Cyclin A / biosynthesis
Cyclin D1 / biosynthesis
Cyclin E / biosynthesis
Cyclin-Dependent Kinase 4 / biosynthesis
Cyclin-Dependent Kinase 6 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
Depsipeptides / chemistry,  pharmacology*
Down-Regulation / drug effects
Humans
Pancreatic Neoplasms / drug therapy*,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin A; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Depsipeptides; 0/sansalvamide A; 136601-57-5/Cyclin D1; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/CDK6 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 6

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


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