Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling

Int J Oncol. 2015 Dec;47(6):2064-72. doi: 10.3892/ijo.2015.3202. Epub 2015 Oct 13.

Abstract

Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Curcumin / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibroblasts / drug effects*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Microscopy, Fluorescence
  • Monoamine Oxidase / metabolism
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / pathology*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Monoamine Oxidase
  • monoamine oxidase A, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Curcumin