LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Simple item page
dc.contributor.authorFuh, Bengen_US
dc.contributor.authorSobo, M.en_US
dc.contributor.authorCen, L.en_US
dc.contributor.authorJosiah, D.en_US
dc.contributor.authorHutzen, B.en_US
dc.contributor.authorCisek, K.en_US
dc.contributor.authorBhasin, D.en_US
dc.contributor.authorRegan, N.en_US
dc.contributor.authorLin, L.en_US
dc.contributor.authorChan, C.en_US
dc.contributor.authorCaldas, H.en_US
dc.contributor.authorDeAngelis, S.en_US
dc.contributor.authorLi, C.en_US
dc.contributor.authorLi, P-K.en_US
dc.contributor.authorLin, J.en_US
dc.date.accessioned2010-11-10T15:55:24Zen_US
dc.date.accessioned2011-05-17T00:49:04Z
dc.date.available2010-11-10T15:55:24Zen_US
dc.date.available2011-05-17T00:49:04Z
dc.date.issued2009-01-13en_US
dc.description.abstractPersistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation. Originally published in British Journal of Cancer 2009 Vol. 110, No. 1en_US
dc.identifier.citationBritish Journal of Cancer; 100:1 p. 106-112en_US
dc.identifier.doi10.1038/sj.bjc.6604793
dc.identifier.pmidPMC2634692en_US
dc.identifier.urihttp://hdl.handle.net/10342/3001en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://www.nature.com/bjc/journal/v100/n1/full/6604793a.htmlen_US
dc.rightsAuthor notified of opt-out rights by Kent Nixon Myers prior to upload of this article.en_US
dc.subjectSTAT3en_US
dc.subjectApoptosisen_US
dc.subjectGlioblastomaen_US
dc.subjectLLL-3en_US
dc.titleLLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma modelen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
LLL-3InhibitsSTAT3Fuhetal.pdf
Size:
254.52 KB
Format:
Adobe Portable Document Format
Download

Collections

Pediatrics