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Mar. Drugs 2007, 5(3), 52-70; doi:10.3390/md503052

Cytotoxicity of the Ascidian Cystodytes dellechiajei Against Tumor Cells and Study of the Involvement of Associated Microbiota in the Production of Cytotoxic Compounds

1,* , 2, 2, 3, 1, 1 and 1
1 División de Microbiología, Universidad de Alicante, 03080 Alicante, Spain 2 Departamento de Ciencias del Mar y Biología Aplicada, Universidad de Alicante, 03080 Alicante, Spain 3 Instituto Biomar, S. A. Pol. Ind. Edificio CEI 2.02, 24231 Onzonilla, León, Spain
* Author to whom correspondence should be addressed.
Received: 18 June 2007 / Accepted: 17 July 2007 / Published: 19 July 2007
(This article belongs to the Special Issue Bioactive Compounds from Marine Microorganisms)
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Many cytotoxic compounds of therapeutic interest have been isolated from marine invertebrates, and some of them have been reported to be of microbial origin. Pyridoacridine alkaloids are the main compounds extracted from the ascidian Cystodytes dellechiajei. Here we describe the in vitro antiproliferative activity against different tumor cell lines of the ascidian extracts and provide some insights on the role of the microbial community associated with the tunicate in the production of these compounds. C. dellechiajei extracts showed remarkably high antiproliferative activity (IC50 ≤5 μg/mL) in human lung carcinoma A-549, colon adenocarcinoma H-116, pancreatic adenocarcinoma PSN-1 and breast carcinoma SKBR3 cell lines. Moreover, we found that the maximum activity was located in the tunic tissue of the colony, which harbours a microbial community. In order to ascertain the involvement of this community in the synthesis of the bioactive compounds different approachs that included culture and culture independent methods were carried out. We undertook a screening for antiproliferative activities of the bacterial isolates from the ascidian, as well as a comprative analysis of the cytotoxic activities and the microbial communities from two color morphs of the ascidian, green and blue. In addition, the changes of the antiproliferative activities and the composition of the microbial communities were studied from ascidians kept in aquaria and treated with antibiotics for one month. Our data obtained from the different experiments did not point out to bacteria as the source of the cytotoxic compounds, suggesting thus an ascidian origin.
Keywords: Ascidian; cytotoxicity; tumor; Cystodytes; bacteria Ascidian; cytotoxicity; tumor; Cystodytes; bacteria
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Martínez-García, M.; Díaz-Valdés, M.; Ramos-Esplá, A.; Salvador, N.; Lopez, P.; Larriba, E.; Antón, J. Cytotoxicity of the Ascidian Cystodytes dellechiajei Against Tumor Cells and Study of the Involvement of Associated Microbiota in the Production of Cytotoxic Compounds. Mar. Drugs 2007, 5, 52-70.

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