Triptolide is a potent
anti-inflammatory agent that also possesses anticancer activity, including against
colorectal cancer (CRC), one of the most frequent
cancers around the world. In order to clarify how
triptolide may be effective against CRC, we analyzed the
proteome and phosphoproteome of CRC cell line HCT116 after incubation for 48 h with the drug (40 nM) or vehicle. Tandem mass tagging led to the identification of 403
proteins whose levels increased and 559 whose levels decreased in the presence of
triptolide. We also identified 3,110 sites in
proteins that were phosphorylated at higher levels and 3,161 sites phosphorylated at lower levels in the presence of the drug. Analysis of these differentially expressed and/or phosphorylated
proteins showed that they were enriched in pathways involving ribosome biogenesis, PI3K-Akt signaling, MAPK signaling,
nucleic acid binding as well as other pathways.
Protein-
protein interactions were explored using the STRING database, and we identified nine
protein modules and 15 hub
proteins. Finally, we identified 57 motifs using motif analysis of phosphosites and found 16 motifs were experimentally verified for known
protein kinases, while 41 appear to be novel. These findings may help clarify how
triptolide works against CRC and may guide the development of novel treatments.