HJ-4, a novel piperine derivative, inhibits tumor growth and angiogenesis via p53 activation and oncogenic pathway inhibition in colorectal cancer models. Sci Rep 2025 Sep 29;15(1):33541
Date
09/30/2025Pubmed ID
41023097Pubmed Central ID
PMC12480698DOI
10.1038/s41598-025-18290-6Scopus ID
2-s2.0-105017630849 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, especially in advanced and metastatic stages where treatment options are limited. HJ-4, a novel piperine derivative, demonstrated strong tumor-selective inhibition. Within safe concentrations (cell viability > 85%), HJ-4 dose-dependently suppressed colony formation and DNA synthesis in CRC cells, showing potent anti-proliferative effects. It also significantly inhibited cell adhesion, wound healing, and invasion, indicating robust anti-migration and anti-invasion properties. In vivo, the CAM model confirmed that HJ-4 reduced both tumor volume and angiogenesis. Mechanistically, HJ-4 activated the p53-dependent apoptosis pathway while suppressing the Wnt/β-catenin axis and E2F transcriptional activity, effectively impeding tumor progression. Overall, HJ-4 exhibits promising tumor specificity and multiple antitumor mechanisms, supporting its potential for clinical development in CRC treatment.
Author List
Zhang L, Liu S, Wang D, Zhang X, Hu Z, Zou X, Li X, Wang X, Xu D, Liu W, Liu BAuthor
Wei Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlkaloidsAnimals
Antineoplastic Agents
Apoptosis
Benzodioxoles
Cell Line, Tumor
Cell Movement
Cell Proliferation
Colorectal Neoplasms
Humans
Mice
Neovascularization, Pathologic
Piperidines
Polyunsaturated Alkamides
Signal Transduction
Tumor Suppressor Protein p53
Xenograft Model Antitumor Assays
