HJ-4, a novel piperine derivative, inhibits tumor growth and angiogenesis via p53 activation and oncogenic pathway inhibition in colorectal cancer models

作者：Luyao Zhang, Shunfang Liu, Dan Wang, Xingyu Zhang, Zhigang Hu, Xun Zou, Xiuming Li, Xiu Jun Wang, Dandan Xu, Wei Liu, B. Liu · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-18290-6 · 被引用次数：1 · 研究领域：Piperaceae Chemical and Biological Studies、Cancer Mechanisms and Therapy、Berberine and alkaloids research

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.