DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jung, Kyung Hee | ko |
dc.contributor.author | Zheng, Hong-Mei | ko |
dc.contributor.author | Jeong, Yujeong | ko |
dc.contributor.author | Choi, Myung-Joo | ko |
dc.contributor.author | Lee, Hyunseung | ko |
dc.contributor.author | Hong, Sang-Won | ko |
dc.contributor.author | Lee, Hee-Seung | ko |
dc.contributor.author | Son, Mi Kwon | ko |
dc.contributor.author | Lee, Soyoung | ko |
dc.contributor.author | Hong, Sungwoo | ko |
dc.contributor.author | Hong, Soon-Sun | ko |
dc.date.accessioned | 2013-03-12T19:01:17Z | - |
dc.date.available | 2013-03-12T19:01:17Z | - |
dc.date.created | 2012-12-31 | - |
dc.date.created | 2012-12-31 | - |
dc.date.issued | 2013-01 | - |
dc.identifier.citation | CANCER LETTERS, v.328, no.1, pp.176 - 187 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | http://hdl.handle.net/10203/103216 | - |
dc.description.abstract | Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway frequently instigates tumorigenesis leading to hepatocellular carcinoma (HCC). We synthesized N-(5-(3-(3-methyl-1,2,4-oxadiazol-3-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (HS-104), a novel PI3K inhibitor, and investigated its in vitro anticancer effect and in vivo capacity in an animal xenograft model. The inhibition of cell growth by HS-104 revealed that it was effective against HCC cell lines. Also, the activation of the AKT/mTOR signal cascade was inhibited by HS-104 treatment in a dose dependent manner. Flow cytometry analysis showed an accumulation of HCC cells in the G2/M phase with concomitant loss of cells in the S phase. The apoptotic effect of HS-104 was accompanied by increased evidence of cleaved caspase-3 and PARP, as well as DNA fragmentation. In angiogenesis studies, HS-104 inhibited the tube formation of vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs), and suppressed microvessel sprouting from a rat aortic ring, ex vivo, and blood vessel formation in the Matrigel plug assay in mice. HS-104 inhibited the expression of the downstream proteins of PI3K including p-AKT, p-mTOR and p-p70S6K in VEGF-induced HUVECs. In the xenograft animal model. HS-104 significantly delayed tumor growth in a dose dependent manner and suppressed the expression of PCNA, CD34 and cleaved caspase-3 in tumor tissue. These studies show that HS-104 inhibited the PI3K/AKT/mTOR signaling pathway resulting in cell growth/angiogenesis inhibition and apoptosis induction. Therefore, HS-104 is considered as a novel drug candidate for the treatment of HCC. (C) 2012 Elsevier Ireland Ltd. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ELSEVIER IRELAND LTD | - |
dc.subject | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject | BIOLOGICAL EVALUATION | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | POOR-PROGNOSIS | - |
dc.subject | CANCER-THERAPY | - |
dc.subject | EXPRESSION | - |
dc.subject | AKT | - |
dc.subject | MUTATIONS | - |
dc.subject | KINASE | - |
dc.subject | MTOR | - |
dc.title | Suppression of tumor proliferation and angiogenesis of hepatocellular carcinoma by HS-104, a novel phosphoinositide 3-kinase inhibitor | - |
dc.type | Article | - |
dc.identifier.wosid | 000311661700021 | - |
dc.identifier.scopusid | 2-s2.0-84868505458 | - |
dc.type.rims | ART | - |
dc.citation.volume | 328 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 176 | - |
dc.citation.endingpage | 187 | - |
dc.citation.publicationname | CANCER LETTERS | - |
dc.identifier.doi | 10.1016/j.canlet.2012.08.005 | - |
dc.contributor.localauthor | Hong, Sungwoo | - |
dc.contributor.nonIdAuthor | Jung, Kyung Hee | - |
dc.contributor.nonIdAuthor | Zheng, Hong-Mei | - |
dc.contributor.nonIdAuthor | Jeong, Yujeong | - |
dc.contributor.nonIdAuthor | Choi, Myung-Joo | - |
dc.contributor.nonIdAuthor | Lee, Hyunseung | - |
dc.contributor.nonIdAuthor | Hong, Sang-Won | - |
dc.contributor.nonIdAuthor | Lee, Hee-Seung | - |
dc.contributor.nonIdAuthor | Son, Mi Kwon | - |
dc.contributor.nonIdAuthor | Lee, Soyoung | - |
dc.contributor.nonIdAuthor | Hong, Soon-Sun | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | HS-104 | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Angiogenesis | - |
dc.subject.keywordAuthor | HCC | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | BIOLOGICAL EVALUATION | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | POOR-PROGNOSIS | - |
dc.subject.keywordPlus | CANCER-THERAPY | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | AKT | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | MTOR | - |
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