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The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma

Adam, C and Baeurle, A and Brodsky, JL and Wipf, P and Schrama, D and Becker, JC and Houben, R (2014) The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma. PLoS ONE, 9 (4).

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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. © 2014 Adam et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Adam, C
Baeurle, A
Brodsky, JLjbrodsky@pitt.eduJBRODSKY0000-0002-6984-8486
Wipf, Ppwipf@pitt.eduPWIPF
Schrama, D
Becker, JC
Houben, R
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSherman, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 2 April 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0092041
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
Date Deposited: 30 Jun 2014 15:48
Last Modified: 02 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/21966

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