Some anti-chronic inflammatory compounds are DNA polymerase λ-specific inhibitors

We previously reported that a phenolic compound, petasiphenol, was a selective inhibitor of DNA polymerase λ (pol λ) in vitro [Biochemistry 41 (2002) 14463]. We found here that another phenolic compound, curcumin (diferuloylmethane), which is known as an anti-chronic inflammatory agent and is structurally quite similar to petasiphenol, was also a potent pol λ inhibitor. The IC₅₀ values of petasiphenol and curcumin were 7.8 and 7.0μM, respectively. Curcumin, as well as petasiphenol, did not influence the activities of replicative DNA polymerases, such as α, γ, δ, and ε, but also showed no effect even on the pol β activity belonging to the X family. Curcumin could prevent the growth of human NUGC-3 cancer cells with LD₅₀ values of 13μM, and halted them at the G2/M phase in the cell cycle, whereas petasiphenol suppressed the cell growth at 66μM and arrested the cells at the G1 phase. These data showed that curcumin and petasiphenol were slightly different functionally. We also previously reported that novel anti-inflammatory terpeno benzoic acids and triterpenoids were inhibitors of mammalian DNA polymerases [Biochem. Biophys. Acta 1475 (2000) 1; Biochem. Biophys. Acta 1596 (2002) 193]. They could also efficiently inhibit the pol λ activity, although they influenced the other polymerase species to the same extent, suggesting that there may be a physiological relationship between pol λ inhibition and anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammation. Expectedly, petasiphenol also showed an anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammatory effect in mice. This finding may provide clues to investigating the molecular mechanism of inflammation.