Document Detail


The marine alkaloid naamidine A promotes caspase-dependent apoptosis in tumor cells.
MedLine Citation:
PMID:  19369860     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis is important for normal development and removal of damaged cells. Evasion of apoptosis by cancer cells is one of the key characteristics of many tumor types. Thus, discovering agents that promote apoptosis in tumor cells could have great therapeutic value. Marine natural products have demonstrated great potential as anticancer agents, and the proapoptotic activity of some of these products is emerging as a potentially useful property for cancer treatments. Using a tumor xenograft assay in rodents, we previously found that the marine alkaloid naamidine A is a potent antitumor agent. In this study, we further characterize the mechanism of action of naamidine A. In cultured tumor cells, we find that naamidine A induces cell death, which is accompanied with annexin V staining, disruption of the mitochondrial membrane potential, and cleavage and activation of caspases 3, 8, and 9, all of which are hallmarks of apoptosis. Furthermore, naamidine A-induced cell death is caspase dependent. We also find that under conditions where naamidine A inhibits tumor xenograft growth, it induces activation of caspase 3, suggesting that apoptosis is part of its antitumorigenic activity in vivo. Apoptosis is not dependent on extracellular signal-regulated kinase 1/2, previously characterized molecular targets of naamidine A, nor does it require functional p53. Our studies support the continued study of naamidine A and its target(s) for the potential development of better clinical treatments for cancer.
Authors:
Daniel V LaBarbera; Katarzyna Modzelewska; Amanda I Glazar; Phillip D Gray; Manjinder Kaur; Tong Liu; Douglas Grossman; Mary Kay Harper; Scott K Kuwada; Nadeem Moghal; Chris M Ireland
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  20     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-01     Completed Date:  2010-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  425-36     Citation Subset:  IM    
Affiliation:
Department of Medicinal Chemistry University of Utah, Salt Lake City, UT 84112, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / isolation & purification,  pharmacology*
Animals
Antineoplastic Agents / isolation & purification,  pharmacology*
Apoptosis / drug effects*
Caspases / metabolism*
Cell Culture Techniques
Cell Cycle / drug effects
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Imidazoles / isolation & purification,  pharmacology*
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms, Experimental / drug therapy,  pathology
Porifera / chemistry*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
AR050102/AR/NIAMS NIH HHS; CA36622/CA/NCI NIH HHS; P30 CA042014/CA/NCI NIH HHS; T32 CA093247/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Antineoplastic Agents; 0/Imidazoles; 110189-06-5/naamidine A; EC 3.4.22.-/Caspases

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


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