Abstract
Five merosesquiterpenes from the sponge Spongia sp., ilimaquinone, smenodiol, dactylospontriol, hydroxymethoxyfarnesylquinone and (-)-cyclospongiaquinone1 were investigated for antiproliferative activity using SRB assay. In HeLa cells, ilimaquinone, smenodiol, dactylospontriol, and (-)-cyclospongiaquinone1 had IC50s of 7.6, 4.3, 3.5, and 27.9µM, respectively, and they all initiated cytotoxicity. On the other hand, hydroxymethoxyfarnesylquinone had an IC50 of 29.2µM and was cytostatic but did not initiate cytotoxicity. Flow cytometric analysis revealed that dactylospontriol and hydroxymethoxyfarnesylquinone caused G0/G1 arrest, suggesting the antiproliferative mechanism relating to DNA damage. The immunofluorescence staining of γH2AX, showed that showed that dactylospontriol and hydroxymethoxyfarnesylquinone initiated DNA double strand breaks. To investigate whether there was an interaction of compound and DNA, the DNA band shift assay was performed; however the retardation of DNA-drug adducts was not observed.
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