Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Adam, C; Baeurle, A; Brodsky, JL; Wipf, P; Schrama, D; Becker, JC; Houben, R.
The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma.
PLoS One. 2014; 9(4):e92041-e92041
Doi: 10.1371/journal.pone.0092041
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- Co-authors Med Uni Graz
- Becker Jürgen Christian
- Schrama David
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, Viral, Tumor - genetics
- Antineoplastic Agents - pharmacology
- Carcinoma, Merkel Cell - drug therapy
- Cell Line, Tumor -
- Cell Transformation, Viral - drug effects
- Gene Expression Regulation, Neoplastic - drug effects
- HSP70 Heat-Shock Proteins - antagonists & inhibitors
- Humans -
- Mice -
- Mice, Inbred NOD -
- Neoplasm Proteins - antagonists & inhibitors
- Polyomavirus - genetics
- Polyomavirus Infections - drug therapy
- Tumor Virus Infections - drug therapy
- Xenograft Model Antitumor Assays -