Identification of 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 as functional targets of the anti-inflammatory and anti-carcinogenic garcinol

Biochem Pharmacol. 2009 May 1;77(9):1513-21. doi: 10.1016/j.bcp.2009.02.005. Epub 2009 Feb 21.


Garcinol (camboginol) from the fruit rind of Guttiferae species shows anti-carcinogenic and anti-inflammatory properties, but the underlying molecular mechanisms are unclear. Here we show that garcinol potently interferes with 5-lipoxygenase (EC and microsomal prostaglandin (PG)E2 synthase (mPGES)-1 (EC, enzymes that play pivotal roles in inflammation and tumorigenesis. In cell-free assays, garcinol inhibited the activity of purified 5-lipoxygenase and blocked the mPGES-1-mediated conversion of PGH2 to PGE2 with IC50 values of 0.1 and 0.3 microM, respectively. Garcinol suppressed 5-lipoxygenase product formation also in intact human neutrophils and reduced PGE2 formation in interleukin-1beta-stimulated A549 human lung carcinoma cells as well as in human whole blood stimulated by lipopolysaccharide. Moreover, garcinol interfered with isolated cyclooxygenase (COX)-1 (EC, IC50 = 12 microM) and with the formation of COX-1-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid and thromboxane B2 in human platelets. In contrast, neither Ca2+-ionophore (A23187)-induced arachidonic acid release in neutrophils nor COX-2 activity in A549 cells or whole blood, measured as formation of 6-keto PGF1alpha, or isolated human recombinant COX-2 were significantly affected by garcinol (< or = 30 microM). Together, the high potency of garcinol to selectively suppress PGE2 synthesis and 5-lipoxygenase product formation provides a molecular basis for the anti-inflammatory and anti-carcinogenic effects of garcinol and rationalizes its therapeutic use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Arachidonate 5-Lipoxygenase / biosynthesis
  • Arachidonic Acid / metabolism
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Escherichia coli / genetics
  • Garcinia / chemistry
  • Humans
  • Intramolecular Oxidoreductases / antagonists & inhibitors*
  • Intramolecular Oxidoreductases / biosynthesis
  • Intramolecular Oxidoreductases / blood
  • Lipoxygenase Inhibitors*
  • Microsomes / drug effects*
  • Microsomes / enzymology
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Prostaglandin-E Synthases
  • Terpenes / isolation & purification
  • Terpenes / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents, Phytogenic
  • Lipoxygenase Inhibitors
  • Terpenes
  • Arachidonic Acid
  • Arachidonate 5-Lipoxygenase
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • garcinol