Curcumin blocks CCL2-induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity

Jeffery G. Herman, Henry L. Stadelman, Charles Roselli

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Expression and activity of CC motif ligand 2 (CCL2) is down-regulated by curcumin, the active phytochemical ingredient of turmeric (Curcuma longa), a dietary supplement often self-prescribed to promote prostate health. CCL2 is a potent chemotactic factor of prostate cancer (PCa) with important roles in development of bone metastasis. The relationship between CCL2 and curcumin, however, has not been studied in PCa. Adhesion, invasion and motility of PC-3 cells were measured in response to exposure to curcumin (30 μM; 18 h), CCL2 (100 ng/ml; 18 h) or PMA (100 ng/ml; 18 h). CCL2 mRNA expression and protein secretion levels were measured by real-time PCR and ELISA respectively. Curcumin significantly blocked CCL2 induced adhesion, invasion and motility. Curcumin also significantly suppressed the mRNA expression and secreted CCL2 protein levels. The addition of PMA, a protein kinase C (PKC) activator, blocked the effects of curcumin, leading to an increase in CCL2 expression as well as an increase in PC-3 cell adhesion, invasion and motility. The introduction of a PKC inhibitor, however, blocked the effects of CCL2. We also found that curcumin, CCL2 and PMA, in part, function through the differential regulation of the proteolytic protein matrix metalloproteinase (MMP)-9. These data indicate a potential mechanism; by which curcumin can block the chemotactic effects of CCL2 on PCa. Curcumin exerts potential anti-metastatic effects in bone-derived PCa cells by blocking CCL2 mediated actions on invasion, adhesion and motility, in part through differential regulation of PKC and MMP-9 signaling.

Original languageEnglish (US)
Pages (from-to)1319-1327
Number of pages9
JournalInternational Journal of Oncology
Volume34
Issue number5
DOIs
StatePublished - 2009

Fingerprint

Curcumin
Down-Regulation
Ligands
Prostatic Neoplasms
Protein Kinase C
Curcuma
Matrix Metalloproteinase 9
Messenger RNA
Proteins
Protein C Inhibitor
Bone Development
Chemotactic Factors
Phytochemicals
Protein Kinase Inhibitors
Dietary Supplements
Cell Adhesion
Cell Movement
Real-Time Polymerase Chain Reaction
Prostate
Enzyme-Linked Immunosorbent Assay

Keywords

  • CCL2
  • Diet
  • MCP-1
  • Nutrition
  • PKC
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Curcumin blocks CCL2-induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity. / Herman, Jeffery G.; Stadelman, Henry L.; Roselli, Charles.

In: International Journal of Oncology, Vol. 34, No. 5, 2009, p. 1319-1327.

Research output: Contribution to journalArticle

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