Curcumin exerts its potential antitumor effects in a context dependent fashion

ABSTRACT: Background Clinical practice demonstrates that anticancer drug effects may strongly vary between different patients. Individual responses to drug action are potentially responsible for adverse effects such as establishment of resistance. Consequently, the understanding of response mechanisms to drug actions is of great relevance. Proteome profiling is a powerful tool for the investigation of cellular responses to drugs. Methods Here, we have investigated the effects of curcumin, a natural remedy with known anti-cancer activities, on breast cancer cells MCF-7, ZR-75-1 and normal mammary fibroblasts as well as co-cultures thereof using proteome profiling. The mammary fibroblasts had been treated before with TGF-beta in order to induce a wound-healing signature known to be representative for the in vivo situation in breast tumors. Results While co-culture alone induced several proteins like ANXA1, S100A4 and SPARC similarly in both breast cancer cells, the majority of proteins regulated upon co-culture differed between MCF-7 and ZR-75-1. Curcumin significantly induced HMOX1 in all single cell models and co-cultures. However, otherwise the curcumin effects differed. In the MCF-7 co-culture, curcumin significantly downregulated RC3H1, a repressor of inflammatory signaling. In the ZR-75-1 co-culture, curcumin significantly downregulated PEG10, an anti-apoptotic protein, and induced RRAGA, a pro-apoptotic protein involved in TNF-alpha signaling. In this model, curcumin also induced AKR1C2, an important enzyme for progesterone metabolism. None of these specific curcumin effects were observed in single cell cultures. Conclusions The present data demonstrate that curcumin induces proteome alterations potentially accounting for its known antitumor effects in a strongly context-dependent fashion.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture, Fibroblast

DISEASE(S): Disease Free,Breast Cancer

SUBMITTER: Christopher Gerner  

LAB HEAD: Christopher Gerner

PROVIDER: PXD008719 | Pride | 2018-06-04

REPOSITORIES: Pride