title: Natural products from aquatic eukaryotic microorganisms for cancer therapy: Perspectives on anti-tumour properties of ciliate bioactive molecules.
abstract: Several modern drugs, including those for cancer therapy, have been isolated from natural sources, are based on natural products and its derivatives, or mime natural products. Some of them are in clinical use, others in clinical trials. The success of natural products in drug discovery is related to their biochemical characteristics and to the technologic methods used to study their feature. Natural compounds may acts as chemo-preventive agents and as factors that increase therapeutic efficacy of existing drugs, thus overcoming cancer cell drug resistance that is the main factor determining the failure in conventional chemotherapy. Water environment, because of its physical and chemical conditions, shows an extraordinary collection of natural biological substances with an extensive structural and functional diversity. The isolation of bioactive molecules has been reported from a great variety of aquatic organisms; however, the therapeutic application of molecules from eukaryotic microorganisms remains inadequately investigated and underexploited on a systematic basis. Herein we describe the biological activities in mammalian cells of selected substances isolated from ciliates, free-living protozoa common almost everywhere there is water, focusing on their anti-tumour actions and their possible therapeutic activity. In particular, we unveil the cellular and molecular machine mediating the effects of cell type-specific signalling protein pheromone Er-1 and secondary metabolites, i.e. euplotin C and climacostol, in cancer cells. To support the feasibility of climacostol-based approaches, we also present novel findings and report additional mechanisms of action using both in vitro and in vivo models of mouse melanomas, with the scope of highlighting new frontiers that can be explored also in a therapeutic perspective. The high skeletal chemical difference of ciliate compounds, their sustainability and availability, also through the use of new organic synthesis/modifications processes, and the results obtained so far in biological studies provide a rationale to consider some of them a potential resource for the design of new anti-cancer drugs.
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università degli Studi della Tuscia, Viterbo, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Catalani
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università degli Studi della Tuscia, Viterbo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Proietti Serafini
authors.affiliation: Unit of Clinical Pharmacology, University Hospital "Luigi Sacco"-ASST Fatebenefratelli Sacco, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zecchini
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università degli Studi della Tuscia, Viterbo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Picchietti
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università degli Studi della Tuscia, Viterbo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fausto
authors.affiliation: School of Sciences and Technologies, Section of Chemistry, Università degli Studi di Camerino, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Marcantoni
authors.affiliation: Laboratory of Protistology and Biology Education, Department of Education, Cultural Heritage and Tourism, Università degli Studi di Macerata, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Buonanno
authors.affiliation: Laboratory of Protistology and Biology Education, Department of Education, Cultural Heritage and Tourism, Università degli Studi di Macerata, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ortenzi
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Università degli Studi di Milano, Italy. Electronic address: cristiana.perrotta@unimi.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Perrotta
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università degli Studi della Tuscia, Viterbo, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Università degli Studi di Milano, Italy. Electronic address: d.cervia@unitus.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Cervia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology* / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods; D056890:Eukaryota; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products
keywords: Anti-tumour molecules; Chemotherapy; Ciliated protozoa; Climacostol; Natural products; Tumour growth