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

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.

The Akt pathway in oncology therapy and beyond (Review)

“…Euplotin C is a secondary metabolite of the marine ciliate Euplotes crassus that has demonstrated marked cytotoxic effects on human cutaneous melanoma cells via the inhibition of the Erk and Akt pathways ( 136 ). A large diversity of plant extracts have demonstrated promising anticancer properties in various cell lines, such as Libidibia ferrea and Celastrus orbiculatus in colorectal cancer ( 137 , 138 ), Astragalus membranaceus , Anthriscus sylvestris and Vernonia amygdalina in breast cancer cells ( 139 - 141 ), Azadirachta indica in prostate cancer ( 142 ), and Fallopia aubertii and Fallopia convolvulus in cervical cancer cells ( 143 ), and these may represent future sources of leading Akt inhibitors.…”

miRNA Modulation and Antitumor Activity by the Extra-Virgin Olive Oil Polyphenol Oleacein in Human Melanoma Cells

“…Apoptosis in 501Mel cells treated with 20 µM OA for 72h was assessed by using Cell Death Detection ELISA plus (#11774425001, Sigma-Aldrich, Milan, Italy), as previously reported by Carpi and colleagues (Carpi et al, 2018).…”

Diclofenac-Derived Hybrids for Treatment of Actinic Keratosis and Squamous Cell Carcinoma

“…Cell viability was measured using the Neutral Red (NR) Assay (N2889, Sigma-Aldrich, Darmstadt, Germany) as previously reported [42]. HaCaT and A431 cell lines were seeded at a density of 5 × 10 4 cells/well in 10% FBS medium in a 96-well plate.…”