Promotion of IL-8 production in PMA-stimulated HL-60 cells by sesquiterpene quinones from a marine sponge, Hippospongia sp.

Abstract

An extract of a marine sponge, Hippospongia sp., collected in Palau has inhibitory activity against colony formation by Chinese hamster V79 cells. Bioassay-guided isolation gave eleven sesquiterpene quinones. Compounds 1–8 inhibited colony formation by V79 cells with EC50 values between 0.6 and 2.8 μmol L−1. Their effects on the production of an inflammatory cytokine, IL-8, in tetradecanoyl phorbol acetate (PMA)-stimulated HL-60 cells were also investigated, because IL-8 production is sometimes correlated with inhibition of cell growth. Ilimaquinone (1) and its 5 epimer (2) had similar activity against V79 cells (EC50 = 2.8 and 2.3 μmol L−1, respectively) but did not modulate IL-8 production even at 10 μmol L−1. Smenospongidine (3) and its 5 epimer (4), smenospongiarine (5) and its 5 epimer (6), and smenospongine (7) and its 5-epimer (8), at 10 μmol L−1, promoted IL-8 production. Compounds 3, 5, and 7 had slightly stronger activity against V79 cells (EC50 = 0.6, 1.7, and 0.8 μmol L−1, respectively) than the corresponding 5 epimers 4, 6, and 8 (EC50 = 0.8, 2.3, and 2.0 μmol L−1, respectively). A similar structure–activity relationship was observed for promotion of IL-8 production. This is the first report of modulation of IL-8 production by these sesquiterpene quinones.