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Updated: Feb 10, 2026

Detection and Isolation of Circulating Melanoma Cells using Photoacoustic Flowmetry
Published on: November 25, 2011
Anticancer Activity of Euplotin C, Isolated from the Marine Ciliate Euplotes crassus, Against Human Melanoma Cells
Sara Carpi1, Beatrice Polini2, Giulio Poli3
1Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy. sara.carpi@unipi.it.
Abstract:
Cutaneous melanoma is the most serious type of skin cancer, so new cytotoxic weapons against novel targets in melanoma are of great interest. Euplotin C (EC), a cytotoxic secondary metabolite of the marine ciliate Euplotes crassus, was evaluated in the present study on human cutaneous melanoma cells to explore its anti-melanoma activity and to gain more insight into its mechanism of action. EC exerted a marked cytotoxic effect against three different human melanoma cell lines (A375, 501Mel and MeWo) with a potency about 30-fold higher than that observed in non-cancer cells (HDFa cells). A pro-apoptotic activity and a decrease in melanoma cell migration by EC were also observed. At the molecular level, the inhibition of the Erk and Akt pathways, which control many aspects of melanoma aggressiveness, was shown. EC cytotoxicity was antagonized by dantrolene, a ryanodine receptor (RyR) antagonist, in a concentration-dependent manner. A role of RyR as a direct target of EC was also suggested by molecular modelling studies. In conclusion, our data provide the first evidence of the anti-melanoma activity of EC, suggesting it may be a promising new scaffold for the development of selective activators of RyR to be used for the treatment of melanoma and other cancer types.
Insights
Euplotin C (EC) shows significant anti-melanoma activity, selectively killing cancer cells while sparing normal cells. This marine compound inhibits key pathways and targets the ryanodine receptor (RyR), offering a potential new treatment for melanoma.
Area of Science:
- Marine Natural Products Chemistry
- Cancer Biology
- Pharmacology
Background:
- Cutaneous melanoma is a severe skin cancer, necessitating the development of novel cytotoxic agents targeting new pathways.
- Marine organisms are a rich source of unique bioactive compounds with therapeutic potential.
Purpose of the Study:
- To evaluate the anti-melanoma activity of Euplotin C (EC), a metabolite from Euplotes crassus.
- To elucidate the mechanism of action of EC in human cutaneous melanoma cells.
- To investigate EC's potential as a novel anti-melanoma therapeutic scaffold.
Main Methods:
- Cytotoxicity assays on human melanoma cell lines (A375, 501Mel, MeWo) and normal human dermal fibroblasts (HDFa).
- Assessment of pro-apoptotic effects and cell migration inhibition.
- Analysis of Erk and Akt pathway inhibition, and interaction with ryanodine receptors (RyR) using molecular modeling and antagonism studies with dantrolene.
Main Results:
- EC demonstrated potent cytotoxicity against melanoma cells, with approximately 30-fold higher potency compared to non-cancer cells.
- EC induced apoptosis and reduced melanoma cell migration.
- EC inhibited Erk and Akt signaling pathways; its cytotoxicity was antagonized by dantrolene, suggesting RyR as a potential direct target.
Conclusions:
- Euplotin C exhibits significant selective anti-melanoma activity.
- EC's mechanism involves apoptosis induction, migration inhibition, and modulation of Erk/Akt pathways, potentially via ryanodine receptor interaction.
- EC represents a promising new scaffold for developing selective RyR activators for melanoma and other cancer treatments.
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