Gambogic acid is cytotoxic to cancer cells through inhibition of the ubiquitin-proteasome system View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-06

AUTHORS

Jenny Felth, Karolina Lesiak-Mieczkowska, Padraig D’Arcy, Caroline Haglund, Joachim Gullbo, Rolf Larsson, Stig Linder, Lars Bohlin, Mårten Fryknäs, Linda Rickardson

ABSTRACT

Gambogic acid (GA), displays cytotoxicity towards a wide variety of tumor cells and has been shown to affect many important cell-signaling pathways. In the present work, we investigated the mechanism of action of GA by analysis of drug-induced changes in gene expression profiles and identified GA and the derivative dihydro GA as possible inhibitors of the ubiquitin-proteasome system (UPS). Both GA and dihydro GA inhibited proteasome function in cells resulting in the accumulation of polyubiquitin complexes. In vitro experiments showed that both GA and dihydro GA inhibited 20S chymotrypsin activity and the inhibitory effects of GA and dihydro GA on proteasome function corresponded with apoptosis induction and cell death. In conclusion, our results show that GA and dihydro GA exert their cytotoxic activity through inhibition of the UPS, specifically by acting as inhibitors of the chymotrypsin activity of the 20S proteasome. More... »

PAGES

587-598

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10637-012-9902-y

DOI

http://dx.doi.org/10.1007/s10637-012-9902-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026659323

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23179339


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