Planta Med 2012; 78 - PI11
DOI: 10.1055/s-0032-1320698

DNA damage initiated by merosesquiterpenes from the sponge Spongia sp

S Kittiwisut 1, S Yuenyongsawad 1, SL Mooberry 2, A Plubrukarn 1
  • 1Marine Natural Products Research Unit, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand
  • 2Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

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.