Synthesis of EPD, an established cytotoxic agent for ovarian cancer cells, and its efficacy in cisplatin and paclitaxel resistant tumor cells

Abstract

Ovarian cancer remains still the leading cause of death of gynaecological malignancy, for the greater part caused by tumour resistance to conventional treatment with cisplatin and paclitaxel. In the past a new compound, EPD, from the plant Calomeria amaranthoides has been isolated and proved to be a potential anti-cancer agent. The sesquiterpene lactone, EPD, or Eremophila-1(10)-11(13)-dien-12,8β-olide, has an alpha-methylene gamma-lactone ring, essential for its apoptotic activity. In order to have sufficient EPD material for further anti-tumour studies, a synthetic route has been developed. Drug combinations with synthesized EPD, cisplatin and paclitaxel were studied in four ovarian cell lines, and normal fibroblasts. EPD showed in particular strength in its effects with the cisplatin resistant cell line COV362 cl 4 and with a paclitaxel resistant cell line A2780. Compared to cisplatin and paclitaxel, less effects of EPD were shown to effect the viability of normal fibroblasts. Synthesized EPD proved to be promising both as an anti-ovarian cancer agent as well as a chemo-sensitizing agent in combination with other anti-cancer drugs. Synthesized EPD will facilitate pre-clinical studies.