Anticancer Potential of Piper retrofractum on Breast Cancer MCF‑7 Cells Via Induction of Cell Death and Reduction of Cell Migration

Background: Piper retrofractum (PR) is traditional medicine in the South‑East country. Objectives: This study examined the PR effects on anticancer and anti‑migratory activity in human breast cancer cells. Materials and Methods: Determination of cancer cell death by the sulforhodamine B, colony formation, flow cytometry methods. Mechanism‑induced cells death was assessed by intracellular reactive oxygen species generation, caspase 3 activity, mitochondrial function, gene expression, and protein expression. Results: The ethanolic extract of PR had higher effects against MCF‑7 cells than DW extract expressing the high levels of piperine. The extracts stimulated cell death in MCF‑7 cells and induced apoptosis with increasing caspase 3 activity, ROS generation, and decreasing mitochondria function. Moreover, the extract also inhibited gene‑related cell proliferation, cdk2, cdk4, and ckd6, and altered protein‑related cell growth, cyclin D1 reduction and p21 induction. Finally, the extract caused inhibition of cells migration by reducing MMP 9 levels. The extracts of PR stimulated MCF‑7 cells death in association with increasing apoptosis and inhibiting cancer cells migration. The induction of cancer cell death may be through modulating mitochondrial function. Conclusion: These extracts may be a novel strategy to improve the efficacy of chemotherapy to treat MCF‑7.