biostudies-literatureZhang LScientific Research Foundation for Returned Scholars of Tongji HospitalChen Xiao-Ping Foundation for the Development of Science and Technology of Hubei ProvinceJiangsu Province Basic Research Program Natural Science FoundationNational Natural Science Foundation of Chinathe Key Program of Basic Science (Natural Science) of Jiangsu ProvinceScientific Research Fund of Tongji Hospital33541https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480698biostudies-literatureUnknown15(1)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, effecScientific reportsHJ-4, a novel piperine derivative, inhibits tumor growth and angiogenesis via p53 activation and oncogenic pathway inhibition in colorectal cancer models.PMC1248069822KJA350001CXPJJH123003-0272023A09822731672022hgry021BK20220063Zou XLi XHu ZWang DZhang XXu DLiu BZhang LLiu SWang XLiu WfalseHJ-4, a novel piperine derivative, inhibits tumor growth and angiogenesis via p53 activation and oncogenic pathway inhibition in colorectal cancer models.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, effec2025-01-01T00:00:00Z2025 Sep2026-06-03T23:28:56.14Z2026-05-03T03:11:55.62ZS-EPMC124806984102309710.1038/s41598-025-18290-6