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Comparison of gene expression profiles of HepG2 cells exposed to Crambescins C1 and A1

María R. Sánchez1*, Juan A. Rubiolo1, Eva Ternon2, Olivier P. Thomas2, Félix V. Vega3, Mercedes R. Vieytes3 and Luis M. Botana1
  • 1 University of Santiago de Compostela, Department of Pharmacology, Faculty of Veterinary, Campus Lugo, Lugo, Spain
  • 2 University of Nice Sophia Antipolis, Nice Institute of Chemistry-PCRE, UMR 7272 CNRS, Faculty of Sciences, Parc Valrose, France
  • 3 University of Santiago de Compostela, Department of Physiology, Faculty of Veterinary, Campus Lugo, Lugo, Spain

Crambescins are guanidine alkaloids firstly isolated in the early 90s from the encrusting Mediterranean sponge Crambe crambe (Schmidt, 1862) (Bondu et al., 2012, Laville et al., 2009, Berlinck et al., 1990). C. crambe derivatives are divided in two families named crambescins and crambescidins (Gerlinck et al., 1992). Although data on the bioactivity of these compounds is scarce, crambescidins have recognized cytotoxic, antifungal, antioxidant, antimicrobial and antiviral activities (Buscema and Van de Vyver, 1985, Jares-Erijman., 1998, Olszewski et al., 2004, Lazaro et al., 2006, Suna et al., 2007, AOKI et al., 2004). Recently we have carefully evaluated the cytotoxic activity of C816 over several human tumor cell types and characterized some of the cellular mechanisms responsible of the anti-proliferative effect of this compound on human liver-derived tumor cells (Rubiolo et al., 2013). Taking this into account, and to better understand the mechanism of action of crambescins and their potential as therapeutic agents, we made a comparative gene expression profiling of HepG2 cells after crambescin C1 (C1) and crambescin A1 (CA1) exposures. Results have shown that C1 induces genes involved in sterol and glucose metabolisms and metabolism involving growth factors. It also down regulates genes mainly involved in cell cycle control, DNA replication, recombination and repair, and drug metabolism. Flow cytometry assays revealed that C1 produces a G0/G1 arrest in HepG2 cell cycle progression. CA1 also down-regulates genes involved in cell cycle regulation, DNA recombination and pathways related to tumor cells proliferation with lower potency when compared to C1.

Acknowledgements

FEDER cofunded-grants. CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01 and Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016, and by Axencia Galega de Innovación, Spain, ITC-20133020 SINTOX, IN852A 2013/16-3 MYTIGAL. CDTIunderISIP Programme, Spain, IDI-20130304 APTAFOOD. European Union’s 7th Framework Programme managed by Research Executive Agency (FP7/2007-2013) under grant agreement Nos. 265409 µAQUA, 315285 CIGUATOOLS and 312184 PHARMASEA.

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Keywords: crambine C1, crambine A1, human tumor cells, Gene Expression Profiling, cell cycle inhibition

Conference: IMMR | International Meeting on Marine Research 2014, Peniche, Portugal, 10 Jul - 11 Jul, 2014.

Presentation Type: Poster Presentation

Topic: BLUE BIOTECH

Citation: Sánchez MR, Rubiolo JA, Ternon E, Thomas OP, Vega FV, Vieytes MR and Botana LM (2014). Comparison of gene expression profiles of HepG2 cells exposed to Crambescins C1 and A1. Front. Mar. Sci. Conference Abstract: IMMR | International Meeting on Marine Research 2014. doi: 10.3389/conf.fmars.2014.02.00061

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Received: 12 May 2014; Published Online: 18 Jul 2014.

* Correspondence: Ms. María R Sánchez, University of Santiago de Compostela, Department of Pharmacology, Faculty of Veterinary, Campus Lugo, Lugo, Lugo, 27002, Spain, maria.roel@usc.es