Piperlongumine Induces Apoptosis and Autophagy via the MAPK/NK-κB Pathway in Human Breast Cancer Cells

Background/Aim: Piperlongumine, a major alkaloid compound found in long pepper (Piper longum L.), is used to treat tumors, malaria, bronchitis, and asthma. This study aimed to investigate the anticancer effects of piperlongumine on SK-BR-3 and T47D human breast cancer cell lines, focusing on its potential to induce apoptosis and autophagy. Materials and Methods: Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine whether piperlongumine reduced breast cancer cell survival. Apoptosis was evaluated through 4′,6-diamidino-2-phenylindole staining for morphological changes and flow cytometry was conducted for quantitative analysis. Acridine orange staining was performed to examine autophagy induction. Western blotting was used to analyze the expression of proteins associated with apoptosis, the mitogen-activated protein kinase (MAPK)/NF-κB pathway, and autophagy. Results: We observed an increase in the apoptosis-related proteins Bax and cleaved poly (ADP-ribose) polymerase, while apoptosis was associated with decreased Bcl-2. Among the MAPK-related proteins, the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) decreased, whereas that of phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated p38 (p-p38) increased. The autophagy-related protein phosphorylated mammalian target of rapamycin (p-mTOR) was decreased, whereas Beclin 1 and LC3-II expression levels increased, indicating autophagy induction. Conclusion: In SK-BR-3 and T47D breast cancer cell lines, piperlongumine induces apoptosis via the MAPK/NF-κB pathway and promotes autophagy. These findings suggests that piperlongumine may serve as a potential therapeutic agent against human breast cancer cells.