Climacostol, a ciliate secondary metabolite with anticancer activity: results from in vitro and in vivo studies Federico Buonanno1, Cristiana Perrotta2, Laura Guerra3, Simona Picchietti3, Anna Maria Fausto3, Enrico Marcantoni4, Simone Giorgi4, Claudio Ortenzi1, Davide Cervia2,3 1Laboratory of Protistology and Biology Education, University of Macerata, 62100 Macerata, Italy 2 Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), Università di Milano, via G.B. Grassi 74, 20157 Milano, Italy 3 Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università della Tuscia, via S. Camillo de Lellis snc, 01100 Viterbo, Italy 4School of Sciences and Technologies, Section of Chemistry, University of Camerino, 62032 Camerino, Macerata, Italy Climacostol is a natural toxic secondary metabolite isolated from the freshwater ciliate Climacostomum virens and belongs to the group of resorcinolic lipids (or alkylresorcinols). Climacostol is stored in ejectable organelles (extrusomes) and it is naturally used by the ciliate for its chemical defense against predators. In addition, it was recently shown that climacostol exerts a potent antimicrobial activity against a panel of bacterial and fungal pathogens, and that it inhibits the growth of mammalian tumor cell lines in a dose-dependent manner by inducing apoptosis via intrinsic pathway. Climacostol is also able to exert a prooxidant effect, inducing plasmid DNA strand breakage and eukaryotic DNA damage in presence of Cu(II) ions. In order to expand these data and due to the availability of the synthetic toxin, we have further analyzed different tumoral and non-tumoral cell lines of the anticancer action of this compound. Cytometry analyses on the B16-F10 mouse melanoma cells indicated that cell proliferation was effectively inhibited by climacostol, with a significant increase of apoptotic cells. The data collected prompted us to investigate the effects of climacostol on in vivo melanoma progression using a B16-F10 allograft transplantation tumor model. The results indicate that climacostol decreased tumour growth and increased the content of apoptotic cells, suggesting that the toxin may be considered for the design of cytotoxic and pro-apoptotic new drugs for melanoma therapy.
Climacostol, a ciliate secondary metabolite with anticancer activity: results from in vitro and in vivo studies
BUONANNO, FEDERICO;ORTENZI, Claudio;
2015-01-01
Abstract
Climacostol, a ciliate secondary metabolite with anticancer activity: results from in vitro and in vivo studies Federico Buonanno1, Cristiana Perrotta2, Laura Guerra3, Simona Picchietti3, Anna Maria Fausto3, Enrico Marcantoni4, Simone Giorgi4, Claudio Ortenzi1, Davide Cervia2,3 1Laboratory of Protistology and Biology Education, University of Macerata, 62100 Macerata, Italy 2 Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), Università di Milano, via G.B. Grassi 74, 20157 Milano, Italy 3 Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università della Tuscia, via S. Camillo de Lellis snc, 01100 Viterbo, Italy 4School of Sciences and Technologies, Section of Chemistry, University of Camerino, 62032 Camerino, Macerata, Italy Climacostol is a natural toxic secondary metabolite isolated from the freshwater ciliate Climacostomum virens and belongs to the group of resorcinolic lipids (or alkylresorcinols). Climacostol is stored in ejectable organelles (extrusomes) and it is naturally used by the ciliate for its chemical defense against predators. In addition, it was recently shown that climacostol exerts a potent antimicrobial activity against a panel of bacterial and fungal pathogens, and that it inhibits the growth of mammalian tumor cell lines in a dose-dependent manner by inducing apoptosis via intrinsic pathway. Climacostol is also able to exert a prooxidant effect, inducing plasmid DNA strand breakage and eukaryotic DNA damage in presence of Cu(II) ions. In order to expand these data and due to the availability of the synthetic toxin, we have further analyzed different tumoral and non-tumoral cell lines of the anticancer action of this compound. Cytometry analyses on the B16-F10 mouse melanoma cells indicated that cell proliferation was effectively inhibited by climacostol, with a significant increase of apoptotic cells. The data collected prompted us to investigate the effects of climacostol on in vivo melanoma progression using a B16-F10 allograft transplantation tumor model. The results indicate that climacostol decreased tumour growth and increased the content of apoptotic cells, suggesting that the toxin may be considered for the design of cytotoxic and pro-apoptotic new drugs for melanoma therapy.File | Dimensione | Formato | |
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