Abstract:
: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.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
LaBarbera DV,Modzelewska K,Glazar AI,Gray PD,Kaur M,Liu T,Grossman D,Harper MK,Kuwada SK,Moghal N,Ireland CMdoi
10.1097/CAD.0b013e32832ae55fsubject
Has Abstractpub_date
2009-07-01 00:00:00pages
425-36issue
6eissn
0959-4973issn
1473-5741journal_volume
20pub_type
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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