Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells

Cancer Lett. 2014 Mar 28;344(2):239-59. doi: 10.1016/j.canlet.2013.11.001. Epub 2013 Nov 23.

Abstract

Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.

Keywords: Apoptosis; Autophagy; Non-small-cell lung cancer; PI3K/Akt/mTOR; Plumbagin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects
  • Naphthoquinones / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Naphthoquinones
  • Phosphoinositide-3 Kinase Inhibitors
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • plumbagin