Curcumin inhibits oral squamous cell carcinoma proliferation and invasion via EGFR signaling pathways

Int J Clin Exp Pathol. 2014 Sep 15;7(10):6438-46. eCollection 2014.

Abstract

Epidermal growth factor receptor (EGFR) is an effective molecular target of anti-cancer therapies. Curcumin is known to inhibit growth, invasion and metastasis by downregulating EGFR expression in some cancer cells. However, the mechanism underlying the effect of curcumin in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we investigated the efficacy of curcumin on proliferation and invasion in SCC-25 cell line. We also explored the effect of curcumin on the activition of EGFR and its downstream signaling molecules Akt, ERK1/2 and STAT3. Furthermore, we examined the inhibition effect of curcumin on EGF-induced EGFR phosphorylation and SCC-25 cells invasion. Our results showed that curcumin inhibited SCC-25 cells proliferation and induced G2/M phase arrest in a dose-dependent manner. Curcumin also inhibited SCC-25 cells invasion and downregulated MMP-2, MMP-9, uPA and uPAR expression. We further revealed that curcumin regulated the p-EGFR and EGFR downstream signaling molecules including Akt, ERK1/2 and STAT3. Finally, our data showed that crucumin reduced the EGF-induced phosphorylation of EGFR and suppressed EGF-triggered SCC-25 cells invasion. Taken together, our results suggest that curcumin reduced SCC-25 cells proliferation and invasion through inhibiting the phosphorylation of EGFR and EGFR downstream signaling molecules Akt, ERK1/2 and STAT3.

Keywords: EGFR; OSCC; curcumin; invasion; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents, Phytogenic
  • Protein Kinase Inhibitors
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Curcumin