Piperine Exhibits Anticancer Potential by Inhibiting the Cell Cycle Progression in Vitro

Background: Leukaemia is a blood-related cancer that is the leading cause of death worldwide. Piperine, a spicy alkaloid found in the spice Piper nigrum, has multifunctional properties. However, its anticancer effects against human chronic myeloid leukemia (CML) cells are yet to be investigated. The present study aims to investigate the anticancer potential of piperine using the human Methods: The anticancer effects of piperine were investigated through 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, generation of reactive oxygen species (ROS), cellular apoptosis, and cell cycle arrest. Additionally, in silico molecular docking was utilized to predict cell death by detecting the binding interactions of piperine with surface proteins of leukemia cells, specifically death receptors 4 (DR4) and death receptors 5 (DR5). Results: Data in the MTT assay showed that piperine treatment inhibited the cellular proliferation of KCL22 cells in a dosedependent manner. Furthermore, nuclear condensation and ROS generation significantly increased when KCL22 cells were treated with piperine. Further study on cell cycle progression showed that piperine treatment inhibited cell cycle progression at G2/M and S phases. In silico molecular docking study showed that piperine has a good binding interaction with both DR4 and DR5. No violation of Lipinski's rule of five was observed. Piperine exhibited drug-likeness properties without toxicity. Conclusions: These findings suggest that piperine may have potential as an anticancer drug against human chronic myeloid leukemia.