Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo

Kapischke M, Fischer T, Tiessen K, Tschesche H, Bruch H-P, Kalthoff H, Kruse M-L (2008)
INTERNATIONAL JOURNAL OF ONCOLOGY 32(1): 273-282.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ;
Abstract
Matrix metalloproteinases (MMPs) play a central role in tissue maintenance, inflammation and during tumour invasion and metastasis. The impact of MMPs in cancer has encouraged the development of novel MMP-inhibitors without adverse effects on the cell viability. We describe here the synthesis and characterisation of a triazine-derivative as a highly potent MMP-inhibitor. The new compound Triazin 17-2 was developed on the basis of a triazine backbone as a well known and well tolerated chemical scaffold. It was de novo synthesized and tested for MMP inhibition in a cell free assay. In vitro characterisation included tests for cell viability, protein expression and MMP activity in PancTu-1 cells. Effectivity of MMP inhibition was analysed in vitro by invasion assay. Triazin 17-2 was investigated in vivo using an orthotopic pancreatic ductal adenocarcinoma (PDAC) xenograft model in SCID/bg mice. Triazin 17-2 proved to have no adverse effects on cell viability in vitro at concentrations effectively inhibiting MMPs in an invasion assay. Application of Triazin 17-2 in vivo in the orthotopic PDAC model in SCID/bg mice showed a significant reduction of primary tumour weight using conservative therapy and inhibition of metastasis in adjuvant therapy. The MMP-inhibitor Triazin 17-2 was developed and characterised in vitro and in vivo. The new compound has no intrinsic activity to kill cells but is very effective in inhibition of MMPs. In vivo testing revealed that MMP-inhibitors are useful tools in anticancer therapy reducing tumour size and invasion even without direct effects on cell survival.
Publishing Year
ISSN
PUB-ID

Cite this

Kapischke M, Fischer T, Tiessen K, et al. Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo. INTERNATIONAL JOURNAL OF ONCOLOGY. 2008;32(1):273-282.
Kapischke, M., Fischer, T., Tiessen, K., Tschesche, H., Bruch, H. - P., Kalthoff, H., & Kruse, M. - L. (2008). Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo. INTERNATIONAL JOURNAL OF ONCOLOGY, 32(1), 273-282.
Kapischke, M., Fischer, T., Tiessen, K., Tschesche, H., Bruch, H. - P., Kalthoff, H., and Kruse, M. - L. (2008). Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo. INTERNATIONAL JOURNAL OF ONCOLOGY 32, 273-282.
Kapischke, M., et al., 2008. Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo. INTERNATIONAL JOURNAL OF ONCOLOGY, 32(1), p 273-282.
M. Kapischke, et al., “Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo”, INTERNATIONAL JOURNAL OF ONCOLOGY, vol. 32, 2008, pp. 273-282.
Kapischke, M., Fischer, T., Tiessen, K., Tschesche, H., Bruch, H.-P., Kalthoff, H., Kruse, M.-L.: Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo. INTERNATIONAL JOURNAL OF ONCOLOGY. 32, 273-282 (2008).
Kapischke, Matthias, Fischer, Tim, Tiessen, Katrin, Tschesche, Harald, Bruch, Hans-Peter, Kalthoff, Holger, and Kruse, Marie-Luise. “Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo”. INTERNATIONAL JOURNAL OF ONCOLOGY 32.1 (2008): 273-282.
This data publication is cited in the following publications:
This publication cites the following data publications:

1 Citation in Europe PMC

Data provided by Europe PubMed Central.

Novel blood biomarkers of pancreatic cancer-associated diabetes mellitus identified by peripheral blood-based gene expression profiles.
Huang H, Dong X, Kang MX, Xu B, Chen Y, Zhang B, Chen J, Xie QP, Wu YL., Am. J. Gastroenterol. 105(7), 2010
PMID: 20571492

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 18097568
PubMed | Europe PMC

Search this title in

Google Scholar