Abstract
Bioassay-guided isolation from the ethanol extract of a marine sponge Theonella sp. collected in Palau yielded bistheonellide A, which strongly inhibited the colony formation of Chinese hamster V79 cells (EC50 = 6.8 nM). Bistheonellide A is an actinpolymerization inhibitor and was suggested to control cytokine production. Therefore, we attempted to detect an effect of this compound on IL-8 production in PMA-stimulated HL- 60 cells. Interestingly, bistheonellide A did not modulate the production of IL-8 under cytotoxic concentrations as determined by LDH analysis. Although the correlation between the inhibition of microtubule assembly and the stimulation of IL-8 production has been observed for several compounds, the polymerization of actin was not related to an IL-8 production in the case of bistheonellide A. It will be suggested that the actin polymerization is not involved in the IL-8 production system.
Highlights
Interleukin-8 (IL-8) is a member of the superfamily of C-X-C chemokines and a chemotactic factor for T cells, neutrophils and basophils [1]
In the course of our studies on biologically active metabolites of marine organisms, we have examined the extracts of marine sponges and ascidians collected in Palau and Indonesia for inhibitory activity against the colony formation of Chinese hamster V79 cells and found that the ethanol extract of a Palauan Theonella sp. revealed strong activity
The inhibitor of the colony formation of V79 cells isolated from the Palauan Theonella sp. was bistheonellide A, which showed an EC50 value of 6.8 nM against V79 cells
Summary
Interleukin-8 (IL-8) is a member of the superfamily of C-X-C chemokines and a chemotactic factor for T cells, neutrophils and basophils [1]. Bioassay-guided isolation from the extract afforded bistheonellide A as the responsible component for the inhibitory activity. The progression of the cell cycle was apparently slowed down or completely inhibited at the G1 phase by treatment with bistheonellide A [8]. We observed the effect of bistheonellide A on IL-8 production in PMA-stimulated HL-60 cells. This system has been established to reveal the relationship between the inhibition of microtubule polymerization and IL-8 production [in preparation]. We describe here the inhibitory activity towards the colony formation of V79 cells and the effects against PMA-stimulated HL-60 cells on IL-8 production, cell proliferation and the cytotoxicity of bistheonelide A.
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