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. doi: 10.1038/s41598-025-18290-6.
Luyao Zhang  #  1 ,  Shunfang Liu  #  2 ,  Dan Wang  #  1 ,  Xingyu Zhang  #  1 ,  Zhongke Hu  1 ,  Xun Zou  1 ,  Xiuming Li  1 ,  Xiujun Wang  1 ,  Dandan Xu  3 ,  Wei Liu  4 ,  Bin Liu  5
Affiliations
  • 1. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
  • 2. Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095, Wuhan, 430030, China.
  • 3. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. [email protected].
  • 4. Cancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. [email protected].
  • 5. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. [email protected].
  • # Contributed equally.
PMID: 41023097 DOI: 10.1038/s41598-025-18290-6
Abstract

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.

Keywords
Angiogenesis inhibition; Chicken embryo chorioallantoic membrane (CAM) model; Colorectal cancer (CRC); HJ-4; Piperine derivative; p53-mediated apoptosis.
Products