TY  - JOUR
A1  - Adam, Christian
A1  - Baeurle, Anne
A1  - Brodsky, Jeffrey L.
A1  - Schrama, David
A1  - Wipf, Peter
A1  - Becker, Jürgen Christian
A1  - Houben, Roland
T1  - The HSP70 Modulator MAL3-101 Inhibits Merkel Cell Carcinoma
N2  - Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future.
KW  - apoptosis
KW  - cancer treatment
KW  - cell staining
KW  - cultured fibroplasts
KW  - heat shock response
KW  - membrans proteins
KW  - polymerase chain reaction
Y1  - 2014
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/11279
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-112795
ER  -