Bioinformatic and experimental fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells.
Determining interacting cellular partners of drugs by chemical proteomic techniques is complex and tedious. Most approaches rely on activity-based probe profiling and compound-centric chemical proteomics. The anti-malarial artemisinin also exerts profound anti-cancer activity, but the mechanisms of action are incompletely understood. In the present investigation, we present a novel approach to identify artemisinin-interacting target proteins. Our approach overcomes usual problems in traditional fishing procedures, because the drug was attached to a surface without further chemical modification. The proteins identified effect among others, cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness. Furthermore, a bioinformatic approach confirmed experimentally identified proteins and suggested a large number of other interacting proteins. Theoretically predicted interaction partners may serve as a starting point to complete the whole set of proteins binding artemisinin.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
T
T
Eichhorn
S
S
Schloissnig
B
B
Hahn
A
A
Wendler
Rolf
R
Mertens
W D
WD
Lehmann
R L
RL
Krauth-Siegel
T
T
Efferth
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
D016588:Anticarcinogenic Agents; D037621:Artemisinins; D009363:Neoplasm Proteins; C031327:artemisinin