Mechanisms of action of triptolide against colorectal cancer: insights from proteomic and phosphoproteomic analyses

Abstract

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.

The therapeutic potential of natural products for treating pancreatic cancer

“…Accumulating evidences revealed that triptolide has a strong antitumor effect in a broad range of cancers, including non-small cell lung cancer (Zhou et al, 2022c), colorectal cancer (Liskova et al, 2022;Song et al, 2022), hepatocellular carcinoma (Li et al, 2022b), acute myeloid leukemia (Chen et al, 2022b;Kang et al, 2022b) and so on.…”

“…For the malignant melanoma treatment, targeted delivery of triptolide was applied with cyclopeptide and αvβ3 integrin-specific exosomes ( Gu et al, 2022 ). Accumulating evidences revealed that triptolide has a strong antitumor effect in a broad range of cancers, including non-small cell lung cancer ( Zhou et al, 2022c ), colorectal cancer ( Liskova et al, 2022 ; Song et al, 2022 ), hepatocellular carcinoma ( Li et al, 2022b ), acute myeloid leukemia ( Chen et al, 2022b ; Kang et al, 2022b ) and so on.…”

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease

“…Triptolide is a diterpenoid extracted from Tripterygium wilfordii Hook. f. which has a variety of biological activities such as antioxidation, immunomodulatory, and anticancer [ 183 , 184 , 185 ]. Some studies have shown that triptolide plays a significant role in the treatment of DKD, and a meta-analysis showed that triptolide significantly reduced albuminuria, blood urea nitrogen, serum creatinine, and urinary albumin/creatinine ratio in DKD animals [ 186 , 187 ].…”

Targeting Aurora-A Inhibits Tumor Progression and Sensitizes Thyroid Carcinoma to sorafenib by decreasing PFKFB3-mediated glycolysis

“…Phosphoproteome and proteome analyses and RNA-seq were performed as previously described (21,22). After adjudgment of proteome data, phosphoproteome data was used to compare the phosphorylation of protein in Aurora-A knockdown TPC1 cells with the control group.…”