Natural products have long served as a valuable source of anticancer therapeutics. Notable examples include the Vinca alkaloids and taxanes, which are derived from the leaves of the Madagascan periwinkle and the needles of the Taxus tree, respectively. These compounds have been integral components of standard-of-care chemotherapy regimens for various cancers over several decades.

One such promising natural compound is EPD (short for eremophila-1(10), 11(13)-dien-12,8β-olide), a sesquiterpene lactone (SL) isolated from the leaves of Calomeria amaranthoides, a plant native to New South Wales and Victoria, Australia. SLs have played significant roles in traditional medicine, and many SLs from diverse natural sources have been investigated for their anticancer properties.

More than a decade ago,¹ Dr. Caroline van Haaften from Leiden, the Netherlands, discovered that EPD extracted from C. amaranthoides inhibits the proliferation of ovarian cancer cell lines, as well as cell lines from other tumor types.^2,3 To facilitate further preclinical development of EPD as a potential anticancer agent, organic chemists at Symeres (the Netherlands) successfully developed a synthetic route to produce EPD. Through various analytical techniques, they confirmed that the synthetic EPD is chemically identical to the natural product and they determined its absolute stereochemistry.

Parallel testing of synthetic and natural EPD on the Oncolines^® cancer cell line panel demonstrated broad antitumor activity across a wide range of cell lines from solid tumors and hematological malignancies. Moreover, comparison of EPD’s inhibitory profile with that of 248 known anticancer agents tested on the same panel suggest that EPD operates via a unique mechanism of action.

These studies, which have been published online in Journal of Natural Products,⁴ merit further investigation of EPD as a novel anticancer therapy for cancers with high unmet medical need, such as ovarian cancer.

References:
[1] van Haaften et al. (2011) Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers. Journal of Experimental & Clinical Cancer Research 30, 29.
[2] van Haaften et al. (2015) Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells. Journal of Experimental & Clinical Cancer Research 34, 38.
[3] van Haaften et al. (2017) Chemosensitivity of BRCA1-mutated ovarian cancer cells and established cytotoxic agents. Int. J. Gynecol. Cancer 27, 1571-1578.
[4] van Haaften et al. (2025) Synthesis and absolute configuration of the sesquiterpene lactone EPD, a natural product with broad antitumor cell activity via a unique mechanism of action. Journal of Natural Products 88, 1766–1771.