HJ-4 is a novel piperine-derived small molecule that demonstrates potent and selective anti-tumor activity in colorectal cancer models. In vitro, HJ-4 significantly inhibits proliferation of HCT116 cells with an IC₅₀ of 15.82 µM—approximately 2.6-fold more potent than piperine—while maintaining low cytotoxicity toward normal 293T cells, indicating favorable tumor selectivity. At 8–32 µM, HJ-4 markedly suppresses colony formation, DNA synthesis, cell adhesion, migration, and invasion in HCT116 and SW480 cells, with superior efficacy compared to the parent compound. Additionally, it disrupts angiogenic network formation, reducing vascular structures to <50% of control levels at higher concentrations. In vivo, using a chicken embryo chorioallantoic membrane (CAM) model, HJ-4 produces dose-dependent tumor growth inhibition, achieving >70% reduction in tumor weight at 32 µM and significantly decreasing vascular density. These findings demonstrate that HJ-4 exerts robust anti-proliferative, anti-metastatic, and anti-angiogenic effects, supporting its potential as a promising lead compound for colorectal cancer therapy.
