Linked Life Data

15130758

Source:http://linkedlifedata.com/resource/pubmed/id/15130758

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2004-5-7
pubmed:abstractText
Cantharidin is an active compound from blister beetles traditionally used for the treatment of cancer. It is known to exert its antitumor activity by inducing apoptosis in cancer cells. However, its signaling pathway still remains unclear. Therefore, we investigated the roles of the mitogen-activated protein kinases (MAPKs) and the tumor suppressor gene, p53, during cantharidin-induced apoptosis in U937 human leukemic cells. Cantharidin effectively activated ERK-1/2, p38 and JNK in U937 cells in a time- and dose-dependent manner. Cantharidin also exhibited a strong cytotoxicity and induced apoptosis in U937 cells. For the evaluation of the role of MAPKs, PD98059, SB202190 and SP600125 were used as MAPK inhibitors for ERK-1/2, p38 and JNK. PD98059 did not affect cantharidin-induced cytotoxicity and apoptosis, whereas SB202190 and SP600125 significantly interfered with cytotoxic and apoptotic activities induced by cantharidin. Cantharidin alone induced the apoptosis by phosphorylation of p53, up-regulation of downstream target genes, MDM2 and p21 and also cleaved caspase-3, whereas SB202190 and SP600125 caused the down-regulation of p53, MDM-2, p21 and cleaved caspase-3 after a co-treatment with cantharidin. Similarly, SB202190 and SP600125 significantly disturbed the caspase-3 activity after a co-treatment with cantharidin by colorimetric assay. Taken together, these results suggest that cantharidin can induce apoptosis by activation of p38 and JNK MAP kinase pathways associated with p53 and caspase-3.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1811-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15130758-Apoptosis, pubmed-meshheading:15130758-Cantharidin, pubmed-meshheading:15130758-Caspase 3, pubmed-meshheading:15130758-Caspases, pubmed-meshheading:15130758-Drug Interactions, pubmed-meshheading:15130758-Enzyme Activation, pubmed-meshheading:15130758-Enzyme Inhibitors, pubmed-meshheading:15130758-Flavonoids, pubmed-meshheading:15130758-G1 Phase, pubmed-meshheading:15130758-Humans, pubmed-meshheading:15130758-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:15130758-MAP Kinase Signaling System, pubmed-meshheading:15130758-Mitogen-Activated Protein Kinases, pubmed-meshheading:15130758-Phosphorylation, pubmed-meshheading:15130758-Tumor Suppressor Protein p53, pubmed-meshheading:15130758-U937 Cells, pubmed-meshheading:15130758-p38 Mitogen-Activated Protein Kinases
pubmed:year
2004
pubmed:articleTitle
Roles of p38 and JNK mitogen-activated protein kinase pathways during cantharidin-induced apoptosis in U937 cells.
pubmed:affiliation
Department of Oncology, Graduate School of East-West Medical Science, Kyunghee University, Yongin 449-701, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't