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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2011-9-13
pubmed:abstractText
Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been shown to exhibit antitumor activity in several human malignant tissues including breast, thyroid, and ovarian cancers. The antitumor activity of ellipticine is thought to be primarily mediated by the induction of DNA damage through the inhibition of topoisomerase II and formation of DNA adducts. The human endometrium is known to express topoisomerase II. However, the apoptogenic activity of ellipticine and the mechanisms underlying its action have not been investigated in endometrial cancer cells. In the present study, exposure to ellipticine (1-10?M) was shown to induce apoptosis in RL95-2 human endometrial cancer cells. Ellipticine-induced cell death was associated with the accumulation of cells in the G2/M phase of the cell cycle and was accompanied by depolarization of the mitochondrial membrane potential, release of cytochrome c and apoptosis-inducing factor (AIF) from the mitochondrial membrane, and caspase activation. The production of intracellular reactive oxygen species (ROS) was increased and sustained at high levels during ellipticine treatment. Subsequent to ROS accumulation, extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were activated in ellipticine-treated cells. Release of AIF from the mitochondria appeared to be affected by caspases, ROS, and ERK. The present data show that the treatment of RL95-2 cells with ellipticine induces apoptosis, ellipticine-induced apoptosis is mediated by ROS and the activation of MAPKs, and release of AIF is involved in a caspase-independent pathway. These results demonstrate the potential of ellipticine as a therapeutic strategy for the treatment of human endometrial cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1879-3185
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-102
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Ellipticine induces apoptosis in human endometrial cancer cells: the potential involvement of reactive oxygen species and mitogen-activated protein kinases.
pubmed:affiliation
Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't