Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation

Brockmann, Anette; Bluwstein, A; Kögel, A; May, S; Marx, A; Tschan, Mario; Brunner, Thomas (2015). Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation. Cell death & disease, 6(6), e1778-e1778. Nature Publishing Group 10.1038/cddis.2015.137

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While many anticancer therapies aim to target the death of tumor cells, sophisticated resistance mechanisms in the tumor cells prevent cell death induction. In particular enzymes of the glutathion-S-transferase (GST) family represent a well-known detoxification mechanism, which limit the effect of chemotherapeutic drugs in tumor cells. Specifically, GST of the class P1 (GSTP1-1) is overexpressed in colorectal tumor cells and renders them resistant to various drugs. Thus, GSTP1-1 has become an important therapeutic target. We have recently shown that thiazolides, a novel class of anti-infectious drugs, induce apoptosis in colorectal tumor cells in a GSTP1-1-dependent manner, thereby bypassing this GSTP1-1-mediated drug resistance. In this study we investigated in detail the underlying mechanism of thiazolide-induced apoptosis induction in colorectal tumor cells. Thiazolides induce the activation of p38 and Jun kinase, which is required for thiazolide-induced cell death. Activation of these MAP kinases results in increased expression of the pro-apoptotic Bcl-2 homologs Bim and Puma, which inducibly bind and sequester Mcl-1 and Bcl-xL leading to the induction of the mitochondrial apoptosis pathway. Of interest, while an increase in intracellular glutathione levels resulted in increased resistance to cisplatin, it sensitized colorectal tumor cells to thiazolide-induced apoptosis by promoting increased Jun kinase activation and Bim induction. Thus, thiazolides may represent an interesting novel class of anti-tumor agents by specifically targeting tumor resistance mechanisms, such as GSTP1-1.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Brockmann, Anette and Tschan, Mario


600 Technology > 610 Medicine & health




Nature Publishing Group




Doris Haefelin

Date Deposited:

14 Jul 2015 14:18

Last Modified:

29 Aug 2021 01:56

Publisher DOI:


PubMed ID:





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