Faculty Collaboration Database

A novel piperine derivative HJJ_3_5 inhibits colorectal cancer progression by modulating EMT signaling pathways. Biochem Biophys Res Commun 2025 Feb 16;749:151323

Date

01/23/2025

Pubmed ID

39842333

DOI

10.1016/j.bbrc.2025.151323

Scopus ID

2-s2.0-85215431954 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Colorectal cancer (CRC) is a fatal cancer prevalent worldwide, and epithelial-mesenchymal transition (EMT) is a key factor in tumor invasion and metastasis. Piperine, a natural alkaloid known for its antitumor properties, faces limitations in clinical use due to its moderate potency. To address this, our team synthesized and validated a new derivative, HJJ_3_5, which has shown potent antitumor activity against CRC cells. We assessed HJJ_3_5's inhibitory effects on the colon cancer cell line HCT116 through MTT, colony formation, and assays for cell migration and invasion. To uncover HJJ_3_5's molecular mechanisms, we utilized transcriptomics, weighted gene co-expression network analysis (WGCNA), and machine learning to identify key EMT-related genes. Western blot and immunofluorescence experiments confirmed the expression changes of these key proteins. Our findings indicate that HJJ_3_5 significantly suppressed the proliferation, migration, and invasion of HCT116 cells in vitro, outperforming piperine. We discovered that HJJ_3_5 downregulated the expression of COL12A1, PJA2, VCAN, MEF2C, DPYD, and DDR2 genes in HCT116 cells, which resulted in a decrease in the EMT regulator SNAI1, thus inhibiting EMT in these cells. In summary, this study presents novel evidence that the piperine derivative HJJ_3_5 inhibits the migration and invasion of colorectal cancer cells through SNAI1-mediated EMT.

Author List

Cheng W, Liu S, He J, Li H, Liu X, Hu Z, Wang X, Wu Z, Xu G, Liu W, Liu B

Author

Wei Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alkaloids
Antineoplastic Agents
Benzodioxoles
Cell Movement
Cell Proliferation
Colorectal Neoplasms
Disease Progression
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Piperidines
Polyunsaturated Alkamides
Signal Transduction