Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, July the 26th 2016, 07:00-10:00

ZORA's new graphical user interface will be relaunched (For further infos watch out slideshow ZORA: Neues Look & Feel). There will be short interrupts on ZORA Service between 07:00am and 10:00 am. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-19962

Imesch, P; Dedes, K J; Furlato, M; Fink, D; Fedier, A (2009). MLH1 protects from resistance acquisition by the histone deacetylase inhibitor trichostatin A in colon tumor cells. International Journal of Oncology, 35(3):631-640.

Accepted Version
View at publisher


The antineoplastic activity of HDAC inhibitors is an unquestionable property of these compounds, but recent studies in tumor cells have revealed the potential of HDAC inhibitors (e.g., suberoylanilide hydroxamic acid SAHA, valproic acid VPA) to cause acquisition of HDAC inhibitor resistance. We report that trichostatin A (TSA), an HDAC inhibitor structurally related to SAHA, causes the acquisition of multidrug resistance transporter-independent and irreversible 3-fold resistance to TSA in MLH1-deficient (absent MLH1 protein expression) but not in MLH1-proficient (expressing MLH1 protein) HCT116 colon tumor cells. This MLH1-deficient subline selected for TSA resistance by stepwise exposures to increasing TSA concentrations exhibited failure in the accumulation of acetylated histones, in p21 induction, and in apoptosis activation. These are cellular responses normally seen in tumor cells treated with HDAC inhibitors. Whereas the absence of acetyl-histone accumulation did not correlate with altered HDAC activity, the absence of apoptosis correlated with reduced expression of (pro-apoptotic) Bax. This TSA-resistant subline was cross-resistant to SAHA and VPA but not to ‘classic’ non-HDAC inhibitor-type anticancer agents such as docetaxel and doxorubicin. These herein presented results expand on a previous study reporting HDAC inhibitor resistance acquisition by SAHA which was independent of the MLH1 expression status. Taken together, the present study identifies TSA, besides SAHA and VPA, as another potential causative of HDAC inhibitor resistance acquisition specifically in MLH1-deficient HCT116 colon tumor cells, and it reveals a possible function of MLH1 protein in protecting colon tumor cells from resistance acquisition by TSA.


8 citations in Web of Science®
7 citations in Scopus®
Google Scholar™



257 downloads since deposited on 29 Jul 2009
55 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
Dewey Decimal Classification:610 Medicine & health
Deposited On:29 Jul 2009 06:52
Last Modified:05 Apr 2016 13:18
Publisher DOI:10.3892/ijo_00000375
Official URL:http://www.spandidos-publications.com/ijo/35/3/631
Related URLs:http://www.spandidos-publications.com/ijo/archive.jsp?journal_id=ijo (Publisher)
PubMed ID:19639184

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page