eprintid: 21966
rev_number: 21
userid: 3671
importid: 2457
dir: disk0/00/02/19/66
datestamp: 2014-06-30 15:48:54
lastmod: 2019-02-02 15:56:47
status_changed: 2014-06-30 15:48:54
type: article
metadata_visibility: show
item_issues_count: 0
eprint_status: archive
creators_name: Adam, C
creators_name: Baeurle, A
creators_name: Brodsky, JL
creators_name: Wipf, P
creators_name: Schrama, D
creators_name: Becker, JC
creators_name: Houben, R
creators_email: 
creators_email: 
creators_email: jbrodsky@pitt.edu
creators_email: pwipf@pitt.edu
creators_email: 
creators_email: 
creators_email: 
creators_id: 
creators_id: 
creators_id: JBRODSKY
creators_id: PWIPF
creators_id: 
creators_id: 
creators_id: 
creators_orcid: 
creators_orcid: 
creators_orcid: 0000-0002-6984-8486
creators_orcid: 
creators_orcid: 
creators_orcid: 
creators_orcid: 
contributors_type: http://www.loc.gov/loc.terms/relators/EDT
contributors_name: Sherman, Michael
title: The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma
ispublished: pub
divisions: sch_as_biosci
divisions: sch_as_chemistry
full_text_status: public
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.
date: 2014-04-02
date_type: published
publication: PLoS ONE
volume: 9
number: 4
refereed: TRUE
id_number: 10.1371/journal.pone.0092041
citation:   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).       
document_url: http://d-scholarship-dev.library.pitt.edu/21966/1/journal.pone.0092041.pdf
document_url: http://d-scholarship-dev.library.pitt.edu/21966/8/licence.txt