Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells

J Pharmacol Sci. 2013;123(2):102-9. doi: 10.1254/jphs.13085fp. Epub 2013 Sep 18.

Abstract

Curcumin is a major yellow pigment and active component of turmeric widely used as dietary spice and herbal medicine. This compound has been reported to be a promising antitumor agent, although the underlying molecular mechanisms are not fully understood yet. In this study, we reported that curcumin inhibited growth of lung adenocarcinoma cells, but had no cytotoxic activity to IMR-90 normal lung fibroblast cells. Curcumin induced autophagy in the A549 human lung adenocarcinoma cell line, evidenced by LC3 immunofluorescence analysis and immunoblotting assays on LC3 and SQSTM1. Moreover, the autophagy inhibitor 3-MA partly blocked the inhibitory effect of curcumin on the growth of A549 cells. Curcumin markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetylCoA carboxylase in A549 cells. At last, pharmacological blockade of the AMPK signaling pathway by compound C and genetic disruption of the AMPK signaling pathway with siRNA-mediated AMPKα1 knockdown impaired the autophagy-inducing effect of curcumin. Collectively, our data suggests that curcumin induces autophagy via activating the AMPK signaling pathway and the autophagy is important for the inhibiting effect of curcumin in lung adenocarcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Acetyl-CoA Carboxylase / metabolism
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Curcumin / pharmacology*
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology*
  • Phosphorylation / drug effects
  • RNA, Small Interfering
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • RNA, Small Interfering
  • PRKAA1 protein, human
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase
  • Curcumin