Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway

PLoS One. 2015 Dec 10;10(12):e0144462. doi: 10.1371/journal.pone.0144462. eCollection 2015.

Abstract

Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244-amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan-Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Adult
  • Aged
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Curcumin / pharmacology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Male
  • Matrix Metalloproteinases / metabolism*
  • Mice, SCID
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neoplasm Metastasis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Adiponectin
  • Anti-Inflammatory Agents, Non-Steroidal
  • NF-kappa B
  • Matrix Metalloproteinases
  • Curcumin

Grant support

This study was supported by the grants NSC 100 - 2320 - B - 037 - 012 - MY2 from the National Science Council of R.O.C, Taiwan to Jong-Rung Tsai. The National Science Council of R.O.C, Taiwan is a government organization which is external to the authors' university. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.