Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wachter, J; Neureiter, D; Alinger, B; Pichler, M; Fuereder, J; Oberdanner, C; Di Fazio, P; Ocker, M; Berr, F; Kiesslich, T.
Influence of five potential anticancer drugs on wnt pathway and cell survival in human biliary tract cancer cells.
Int J Biol Sci. 2012; 8(1):15-29
Doi: 10.7150/ijbs.8.15
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- Co-Autor*innen der Med Uni Graz
- Pichler Martin
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- Abstract:
- Background: The role of Wnt signalling in carcinogenesis suggests compounds targeting this pathway as potential anti-cancer drugs. Several studies report activation of Wnt signalling in biliary tract cancer (BTC) thus rendering Wnt inhibitory drugs as potential candidates for targeted therapy of this highly chemoresistant disease. Methods: In this study we analysed five compounds with suggested inhibitory effects on Wnt signalling (DMAT, FH535, myricetin, quercetin, and TBB) for their cytotoxic efficiency, mode of cell death, time- and cell line-dependent characteristics as well as their effects on Wnt pathway activity in nine different BTC cell lines. Results: Exposure of cancer cells to different concentrations of the compounds results in a clear dose-dependent reduction of viability for all drugs in the order FH535 > DMAT > TBB > myricetin > quercetin. The first three substances show high cytotoxicity in all tested cell lines, cause a direct cytotoxic effect by induction of apoptosis and inhibit pathway-specific signal transduction in a Wnt transcription factor reporter activity assay. Selected target genes such as growth-promoting cyclin DI and the cell cycle progression inhibitor p27 are down- and up-regulated after treatment, respectively. Conclusions: Taken together, these data demonstrate that the small molecular weight inhibitors DMAT, F535 and TBB have a considerable cytotoxic and possibly Wnt-specific effect on BTC cell lines in vitro. Further in vivo investigation of these drugs as well as of new Wnt inhibitors may provide a promising approach for targeted therapy of this difficult-to-treat tumour.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use
- Benzimidazoles - chemistry Benzimidazoles - pharmacology Benzimidazoles - therapeutic use
- Biliary Tract Neoplasms - drug therapy Biliary Tract Neoplasms - metabolism Biliary Tract Neoplasms - pathology
- Cadherins - genetics
- Cell Line, Tumor -
- Cell Survival - drug effects
- Clinical Trials as Topic -
- Cyclin D1 - genetics
- Flavonoids - chemistry Flavonoids - pharmacology Flavonoids - therapeutic use
- Gene Expression Regulation, Neoplastic - drug effects
- Genes, p53 -
- Humans -
- Ki-67 Antigen - genetics
- Proliferating Cell Nuclear Antigen - genetics
- Quercetin - chemistry Quercetin - pharmacology Quercetin - therapeutic use
- RNA, Messenger - metabolism
- Sulfonamides - chemistry Sulfonamides - pharmacology Sulfonamides - therapeutic use
- Triazoles - chemistry Triazoles - pharmacology Triazoles - therapeutic use
- Vimentin - genetics
- Wnt Signaling Pathway - drug effects Wnt Signaling Pathway - genetics
- beta Catenin - genetics
- Find related publications in this database (Keywords)
- Biliary Tract Cancer
- Wnt pathway
- pharmacological inhibition
- Cytotoxicity
- Apoptosis