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Differential inhibition of transmembrane 4 L six family member 5 (TM4SF5)-mediated tumorigenesis by TSAHC and sorafenib.
Cited 15 time in
Web of Science
Cited 16 time in Scopus
- Authors
- Issue Date
- 2011-02
- Publisher
- Landes Bioscience
- Citation
- CANCER BIOLOGY & THERAPY Vol.11 No.3, pp. 330-336
- Keywords
- 자연과학 ; contact inhibition ; anti-tumorigenic reagent ; anti-tumorigenic reagent ; sorafenib ; TM4SF5
- Abstract
- Two separate clinical studies of advanced hepatocarcinoma patients recently reported that the multikinase inhibitor
sorafenib (nexavar) could extend survival of the patients only by 2–3 months. We also previously demonstrated that
4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC) blocks the multilayer growth and migration mediated by
TM4SF5, which is highly expressed in approximately 80% of Korean hepatocarcinoma patients. Therefore, we wondered
how TSAHC might be different from sorafenib to deal with hepatocarcinoma in terms of the therapeutic characteristics
including specificity for TM4SF5. TM4SF5 is previously shown to mediate tumorigenesis through cytosolic p27Kip1-
mediated inactivation of RhoA, epithelial-mesenchymal transition, multilayer growth, migration, invasion and tumor
angiogenesis. In this study, TSAHC and two derivatives showed similar antagonistic activities against TM4SF5-mediated
signaling and multilayer growth in vitro and anti-tumorigenic activity even in early stages of TM4SF5-mediated tumor
formation in nude mice. Meanwhile, sorafenib was only effective much later in tumorigenesis in vivo and affected in vitro
proliferation in a TM4SF5-independent manner. Altogether, these observations suggest that TSAHC may be a promising
anti-tumorigenic reagent, especially against TM4SF5-mediated hepatocarcinoma.
- ISSN
- 1538-4047
- Language
- English
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