Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

Int J Mol Sci. 2016 Apr 23;17(4):616. doi: 10.3390/ijms17040616.

Abstract

Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

Keywords: apoptosis; cell cycle arrest; human oral squamous cell carcinoma; piperlongumine; senescence.

MeSH terms

  • Acetylcysteine / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Fragmentation / drug effects
  • Dioxolanes / pharmacology*
  • Humans
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p21
  • Dioxolanes
  • Reactive Oxygen Species
  • Caspase 3
  • piperlongumine
  • Acetylcysteine