Curcumin inhibits lipoxygenase by binding to its central cavity: Theoretical and X-ray evidence

Many lipoxygenase inhibitors including curcumin are currently being studied for their anti-carcinogenic properties. Curcumin is a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of the plant Curcuma longa that possesses anti-inflammatory properties and inhibits canc er formation in mice. Recently it was shown that the soybean lipoxygenase L 1 catalyzed the oxygenation of curcumin and that curcumin can act as a lipo xygenase substrate. In the current study, we investigated the fate of curcu min when used as a soybean lipoxygenase L3 substrate. By use of X-ray diffr action and mass spectrometry, we found an unoccupied electron mass that app ears to be an unusual degradation product of curcumin (4-hydroxyperoxy-2-me thoxyphenol) located near the soybean L3 catalytic site. Understanding how curcumin inhibits lipoxygenase may help in the development of novel anti-ca ncer drugs used for treatment where lipoxygenases are involved.