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Marine Drugs
Volume 16
Issue 5
10.3390/md16050166
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Article

Anticancer Activity of Euplotin C, Isolated from the Marine Ciliate Euplotes crassus, Against Human Melanoma Cells

by
Sara Carpi
1,*,†,
Beatrice Polini
1,†,
Giulio Poli
2,
Gabriela Alcantara Barata
1,
Stefano Fogli
3,
Antonella Romanini
4,
Tiziano Tuccinardi
1,
Graziano Guella
5,
Francesco Paolo Frontini
6,
Paola Nieri
1,‡ and
Graziano Di Giuseppe
6,‡
1
Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy
2
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
3
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
4
Medical Oncology Unit, University Hospital of Pisa, via Roma 67, 56126 Pisa, Italy
5
Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, Via Sommarive 4, 38123 Povo, Trento, Italy
6
Unit of Zoology-Anthropology, Department of Biology, University of Pisa, via A. Volta 4, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Mar. Drugs 2018, 16(5), 166; https://doi.org/10.3390/md16050166
Received: 24 April 2018 / Revised: 8 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue Terpenoids from Marine Organisms)
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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. View Full-Text
Keywords: euplotin C; cutaneous melanoma; marine drug; Euplotes crassus; sesquiterpenoid; protist; ryanodine receptor euplotin C; cutaneous melanoma; marine drug; Euplotes crassus; sesquiterpenoid; protist; ryanodine receptor
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MDPI and ACS Style

Carpi, S.; Polini, B.; Poli, G.; Alcantara Barata, G.; Fogli, S.; Romanini, A.; Tuccinardi, T.; Guella, G.; Frontini, F.P.; Nieri, P.; Di Giuseppe, G. Anticancer Activity of Euplotin C, Isolated from the Marine Ciliate Euplotes crassus, Against Human Melanoma Cells. Mar. Drugs 2018, 16, 166. https://doi.org/10.3390/md16050166

AMA Style

Carpi S, Polini B, Poli G, Alcantara Barata G, Fogli S, Romanini A, Tuccinardi T, Guella G, Frontini FP, Nieri P, Di Giuseppe G. Anticancer Activity of Euplotin C, Isolated from the Marine Ciliate Euplotes crassus, Against Human Melanoma Cells. Marine Drugs. 2018; 16(5):166. https://doi.org/10.3390/md16050166

Chicago/Turabian Style

Carpi, Sara; Polini, Beatrice; Poli, Giulio; Alcantara Barata, Gabriela; Fogli, Stefano; Romanini, Antonella; Tuccinardi, Tiziano; Guella, Graziano; Frontini, Francesco P.; Nieri, Paola; Di Giuseppe, Graziano. 2018. "Anticancer Activity of Euplotin C, Isolated from the Marine Ciliate Euplotes crassus, Against Human Melanoma Cells" Mar. Drugs 16, no. 5: 166. https://doi.org/10.3390/md16050166

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