Piperine Triggers Apoptosis of Human Oral Squamous Carcinoma Through Cell Cycle Arrest and Mitochondrial Oxidative Stress

ABSTRACT

Piperine is a nitrogenous pungent substance exhibiting multifunctional pharmacological properties. However, the mechanism underlying its anticancer potential is not well elucidated in human oral squamous carcinoma (KB) cell line. The anticancer potential of piperine was evaluated through potent biomarkers viz. reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP). In addition, cell cycle kinetics and caspases-3 activity were also carried out to confirm anticancer activity of piperine. Results showed that various concentrations (25–300 μM) of piperine exposure reduced the cell viability of KB cells significantly (P < 0.01). Piperine induced significant (P < 0.01) dose-related increment in ROS production and nuclear condensation. Moreover, piperine stimulated cell death by inducing loss of MMP, and caspase-3 activation. Cell cycle study revealed that piperine arrested the cells in G2/M phase and decreased the DNA content. Findings of this study suggest the efficacy of piperine in inducing cell death via the decrease in MMP and ROS liberation followed by caspase-3 activation and cell cycle arrest. Further assessment of the anticancer potency of piperine is needed for anticancer drug development.

Declaration of interests

The authors declare that they have no potential conflicts of interest.

Funding

The authors acknowledge support from Uttar Pradesh Council of Science and Technology (UPCST, Lucknow) (No. CST/SERPD/D-299) and University Grant Commission (UGC, New Delhi) (F.No.42–500/2013SR) in the form of research grant. We express our thanks to Mr. A.L. Vishwakarma, SAIF-Division, CSIR-CDRI for the flow cytometry. Sahabjada Siddiqui is thankful to ICMR, New Delhi, India for the award of Research Associateship (No. 45/26/2013/BMS/TRM; IRIS ID No. 2013-16160).