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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-10-20
pubmed:abstractText
Although pectenotoxin-2 (PTX-2) is known to modify the actin cytoskeleton, very little is known about its apoptosis mechanism. In this study, we investigated whether PTX-2 induces apoptotic effects through suppression of the NF-kappaB signaling pathway in several leukemia cell types. PTX-2 significantly induced growth inhibition and apoptosis in a dose-dependent manner. Treatment with PTX-2 also significantly increased caspase-3 activity and poly (ADP-ribose) polymerase (PARP) cleavage, however caspase-3 inhibitor z-DEVD-fmk significantly inhibited PTX-2-induced cell death. These data suggest that the activation of caspase-3 is associated with PTX-2-induced apoptosis. NF-kappaB has also been shown to inhibit apoptosis in response to chemotherapeutic agents. As examined by the DNA-binding of NF-kappaB activation, we found that PTX-2 suppressed constitutive NF-kappaB activation and determined by p65 and p50 nuclear translocation, and IkappaBalpha degradation through dephosphorylation of Akt. Attenuation of constitutive NF-kappaB activity by pretreatment with pyrrolidine dithiocarbamate (PDTC), an NF-kappaB nuclear translocation inhibitor, induced significantly apoptosis in the presence of PTX-2. In addition, treatment of PTX-2 down-regulated NF-kappaB-dependent gene expression, Cox-2, IAP-1, IAP-2 and XIAP, at the transcriptional and translational level. Taken together, these results suggest that anti-cancer activities induced by PTX-2 may be mediated in part through suppression of constitutive NF-kappaB activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1872-7980
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-33
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Pectenotoxin-2 abolishes constitutively activated NF-kappaB, leading to suppression of NF-kappaB related gene products and potentiation of apoptosis.
pubmed:affiliation
Department of Microbiology, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't