The novel piperine derivative MHJ-LN inhibits breast cancer by inducing apoptosis via p53 activation.

Triple-negative breast cancer (TNBC) is characterized by high aggressiveness and recurrence rates due to the lack of effective treatment options. Piperine, a natural alkaloid extracted from black pepper, has demonstrated significant anticancer potential in recent years. Therefore, developing piperine derivatives to enhance its anticancer effects holds critical clinical significance. In this study, a novel piperine derivative, MHJ-LN, was designed and synthesized. Its anticancer effects against TNBC were systematically evaluated through in vitro and in vivo experiments. The MTT assay, EdU incorporation assay, and colony formation assay were employed to assess the impact of MHJ-LN on TNBC cell proliferation. Tumor cell adhesion, scratch wound healing, and Transwell invasion assays were performed to analyze the antitumor activity of MHJ-LN. Additionally, apoptosis was detected using YO-PRO-1/PI staining, and immunofluorescence combined with Western blotting was used to assess the expression of p53 pathway-related proteins. MHJ-LN exhibited significant antitumor activity in the TNBC xenograft model. Its mechanism of antitumor action was found to depend on the activation of the MDM2-p53 pathway, effectively blocking G1/S cell cycle progression and inducing apoptosis and cell cycle arrest. This research suggests that the piperine derivative MHJ-LN shows significant potential as an effective therapy targeting breast cancer.