Abstract
Purpose :
Metastatic uveal melanoma (MUM) is a poor prognosis cancer wherein approximately 85% of patients diagnosed do not survive beyond one year. There is no standard of care for MUM. Therefore, it is vital to understand and identify novel pharmacological based drugs for MUM. Ergolide, a sesquiterpene lactone isolated from the flowers of Inula species (a medicinal herb), exerts anti-cancer properties. The objective of this study is to: 1) evaluate whether Ergolide reduced MUM cell survival/viability in vitro and in vivo; and 2) understand the Ergolide mechanism of action.
Methods :
Clonogenic cell survival assays assessed the ability of uveal melanoma (UM) cells derived from primary (Mel285 and Mel270) and metastatic (OMM2.5) tumours to proliferate following treatment with Ergolide. Cells were treated with 1, 5 or 10 µM Ergolide (N = 3) for 96 hours and additionally cultured for 10 days with fresh media. Dil labelled OMM2.5 cells were transplanted into the perivitelline space of 2 days old zebrafish larvae, treated with 0.5% DMSO or 2.5 µM Ergolide for 3 days and analysed for changes in primary xenograft cell fluorescence. Methods to isolate extracellular vesicles from OMM2.5 cells and UM patient samples are being optimised.
Results :
Ergolide treatment resulted in a dose dependent, significant reduction (ranging from 48.5 - 99.9%; p < 0.02) in cell colony proliferation across all three UM cell lines. In vivo, in zebrafish OMM2.5 xenograft models, 2.5 µM Ergolide treatment averaged a 56% regression (p < 0.0001) of normalized primary xenograft fluorescence compared to vehicle controls.
Conclusions :
Our findings suggest that Ergolide is capable of preventing UM/MUM cell survival in vitro; and reduces OMM2.5 primary xenograft fluorescence in vivo that needs to be further explored. Future studies will investigate 1) the mechanism of action of Ergolide in vitro through proteome profiling, and 2) changes to the molecular properties of extracellular vesicles isolated from OMM2.5 cells treated with Ergolide.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.