Hexa-, hepta- and nonaprenylhydroquinone isolated from marine sponges Sarcotragus muscarum and Ircinia fasciculata induce apoptosis in Hct116 cells

Marine organisms have proved to be a source of potent pharmacologically active compounds [1–3]. Three polyprenyl-1,4-hydroquinone derivates (hexaprenyl-1,4-hydroquinone 1, heptaprenyl-1,4-hydroquinone 2 and nonaprenyl-1,4-hydroquinone 3 were isolated from the Zoobenthos-inhabiting sponges Sarcotragus muscarum (Porifera: Demospongiae) and Ircinia fasciculata (Pallas) from the Aegean Sea. We analysed cytotoxic effects of these substances against three tumour cell lines: Hexaprenylhydroquinone exerted highest toxicity in all cell lines (H4IIE, HepG2 and Hct116 cells, respectively; H4IIE IC₅₀ approx. 2.5µM (1) compared to 25µM (2, 3), MTT assay, 24h incubation). The mode of cell death was further analysed in Hct116 cells showing an apoptotic mode of cell death by these compounds (caspase-3 activation, nuclear fragmentation). Further experiments showed that the compounds exerted prominent antioxidative activity comparable to that of Trolox in the TEAC assay. In conclusion, the prenylated hydroquinones isolated from the marine sponges S. muscarum and I. fasciculata showed prominent cytotoxic activities against various cancer cell lines, exhibiting an apoptotic cell death in Hct116 cells. This may lead to the generation of new lead substances in cancer therapy.

Acknowledgements This research was supported by a grant (SBAG104S109) from TÜBİTAK and JÜLİCH

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