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

Abstract

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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.

Keywords

• Gene Expression Profiling
• human tumor cells
• cell cycle inhibition
• crambine C1
• crambine A1