Linked Life Data

19010909

Source:http://linkedlifedata.com/resource/pubmed/id/19010909

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2008-11-17
pubmed:abstractText
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Systemic treatments for HCC have been largely unsuccessful. OSU-03012 is a derivative of celecoxib with anticancer activity. The mechanism of action is presumably 3-phosphoinositide-dependent kinase 1 (PDK1) inhibition. This study investigated the potential of OSU-03012 as a treatment for HCC. OSU-03012 inhibited cell growth of Huh7, Hep3B, and HepG2 cells with IC(50) below 1 mumol/L. In Huh7 cells, OSU-03012 did not suppress PDK1 or AKT activity. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and flow cytometry analysis indicated that OSU-03012 did not induce cellular apoptosis. Instead, morphologic studies by light and electron microscopy, as well as special biological staining with monodansylcadaverine, acridine orange, and microtubule-associated protein 1 light chain 3, revealed OSU-03012-induced autophagy of Huh7 cells. This OSU-03012-induced autophagy was inhibited by 3-methyladenine. Moreover, reactive oxygen species (ROS) accumulation was detected after OSU-03012 treatment. Blocking ROS accumulation with ROS scavengers inhibited autophagy formation, indicating that ROS accumulation and subsequent autophagy formation might be a major mechanism of action of OSU-03012. Daily oral treatment of BALB/c nude mice with OSU-03012 suppressed the growth of Huh7 tumor xenografts. Electron microscopic observation indicated that OSU-03012 induced autophagy in vivo. Together, our results show that OSU-03012 induces autophagic cell death but not apoptosis in HCC and that the autophagy-inducing activity is at least partially related to ROS accumulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9348-57
pubmed:meshHeading
pubmed-meshheading:19010909-Adenine, pubmed-meshheading:19010909-Animals, pubmed-meshheading:19010909-Apoptosis, pubmed-meshheading:19010909-Autophagy, pubmed-meshheading:19010909-Carcinoma, Hepatocellular, pubmed-meshheading:19010909-Cell Line, Tumor, pubmed-meshheading:19010909-Humans, pubmed-meshheading:19010909-Liver Neoplasms, pubmed-meshheading:19010909-Male, pubmed-meshheading:19010909-Mice, pubmed-meshheading:19010909-Mice, Inbred BALB C, pubmed-meshheading:19010909-Microtubule-Associated Proteins, pubmed-meshheading:19010909-Protein Kinase Inhibitors, pubmed-meshheading:19010909-Protein-Serine-Threonine Kinases, pubmed-meshheading:19010909-Pyrazoles, pubmed-meshheading:19010909-Reactive Oxygen Species, pubmed-meshheading:19010909-Sulfonamides, pubmed-meshheading:19010909-Xenograft Model Antitumor Assays
pubmed:year
2008
pubmed:articleTitle
OSU-03012, a novel celecoxib derivative, induces reactive oxygen species-related autophagy in hepatocellular carcinoma.
pubmed:affiliation
Institute of Toxicology, National Taiwan University, Taipei 10016, Taiwan, Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't