The novel Piperine derivative YL-1-9 exhibits anti-breast Cancer effects by inducing apoptosis via the p53/p21 pathway

Abstract

The tumor suppressor protein p53 plays a crucial role in the pathogenesis of breast cancer; however, its function is often compromised due to MDM2 overexpression or mutations in the p53 gene, which occurs in approximately 30–35 % of breast cancer cases. Piperine, a natural bioactive compound, has shown potential in inhibiting breast cancer cell growth by upregulating p53 expression. However, its clinical application is hindered by poor bioavailability, potential toxicity, and the risk of undesirable drug interactions. In the present study, a novel derivative of Piperine, YL-1-9, was synthesized and evaluated for its anticancer activity against breast cancer. YL-1-9, a bicyclic amide derivative of Piperine, was evaluated for antitumor effects both in vitro and in vivo using MTT assays and the chick embryo chorioallantoic membrane (CAM) model. Further investigations into its effects on breast cancer cell clonogenicity, adhesion, invasion, and migration were conducted through colony formation assays, EdU assays, cell adhesion and invasion studies, and wound healing experiments. Western blot analysis was performed to elucidate the effects of YL-1-9 on the cell cycle and apoptosis, which were further validated using YO-PRO-1 and propidium iodide dual staining. YL-1-9 significantly inhibited breast cancer cell proliferation, adhesion, invasion, and migration, while inducing cell cycle arrest and promoting apoptosis. Mechanistically, YL-1-9 downregulated critical proteins in the CDK4/6-cyclin D-Rb-E2F pathway and the Caspase 3/Bax/Bcl-2 apoptosis signaling pathway. These findings position YL-1-9 as a promising candidate for breast cancer therapy; however, further clinical studies are necessary to fully assess its therapeutic potential.