In 1972 a diastereoisomer of EPD, (3aβ,4aα,5α,9αβ)-3a,4,4a,5,6,7,9,9a octahydro4a,5-dimethyl-3-methylenenaphtho[2,3-b]furan-2(3H)-2-one, has been described as “”naphthofuranone”" by the National Cancer Institute (NCI) in their “”in vivo”" anti-tumor screening data, testing the drug against P388 Leukemia in CD2F1 mice, however, no final conclusive results were reported [17]. An allergenic sesquiterpene lactone, Alantolactone, found in “”Elfdock”" Inula helenium has been shown to be toxic to leukocytes. Although with the same molecular weight and molecular formula as EPD it belongs to the eudesmanolide structure sub-type [18]. This SL has

a different chemical structure from EPD, with different positions GSK2126458 in vivo of one methyl and one double Vistusertib cost bond. In the present study, EPA, the other sesquiterpene isolated and identified, did not show Selleckchem 7-Cl-O-Nec1 cytotoxic effects on the ovarian cancer at concentrations up to 10 μg/mL of purified compound. Besides the cytotoxic effects of the crude extract of C. amaranthoides with clear effects at 10 μg/mL (cell

reduction >80%), the isolated biologically active compound EPD has been shown to have high cytotoxicity (>50%) for ovarian cancer cells at lower concentrations of 5 μg/mL (72 hours) and increased (> 60%) with a dose of 10 μg/mL (at 48 hours; Table 1). Interestingly, both the crude plant extract and EPD did show only a slight cytotoxic effect (20%-30%) on normal fibroblasts in vitro at a concentration of 10 μg/mL (at 72 hours). The in vivo pilot experiment with BALB/c nude mice (Table 2, Figure 2) did show that both EPD and Cisplatin reduced the size of the abdomen. The difference, however, was that mice treated with Cisplatin were in poor condition and became wasted compared with the EPD treated mice. Ovarian cancer has a poor prognosis. With more than 60% of the patients presenting the disease in stage III or IV, combination chemotherapy with Platinum and Taxol after cytoreductive surgery gives the most tolerated standard regimen [19, 20]. In spite of the introduction of new drugs into the management of ovarian cancer there is still need for more novel treatments. Conclusion The compound

EPD has shown unique cytotoxicity effects Beta adrenergic receptor kinase on both in vitro (ovarian cancer cell lines) as well as in vivo (mice). Interestingly, it had low cytotoxic effects on normal cells. More studies in vivo are required to verify the mechanisms and mode of action of EPD, and to further validate the potential of EPD as an anti-cancer drug in ovarian cancer and other types of cancer. Acknowledgements We thank Fred Romijn, Wouter Temmink (LUMC, Leiden) and Alma Edelman (RDGG, Delft) for their technical assistance. A European patent was recently granted for the crude extract of Calomeria amaranthoides: EP 1843759 References 1. Ventenat EP: ‘Jardin de la Malmaison’. Volume 1,2. De Crapelet and Orchard (Paris); 1804. 2. Smith JE: ‘Exotic botany’. Volume 1. Taylor R & Co. (London); 1804. 3.