Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 87
Role of plasma membrane fluidity in cisplatin-induced apoptosis in HT29 human colon
cancer cells
Amélie Rebillard1, Odile Sergent2, Olivier Meurette1, Gwénaëlle Le Moigne1, Morgane
Gorria1, Laurent Vernhet1, Dominique Lagadic-Gossmann1 & Marie-Thérèse
Dimanche-Boitrel1*
1INSERM UMR 620 & 2Laboratoire de Biologie Cellulaire et Végétale, Faculté de
Pharmacie, Université Rennes 1, 2 av du Prof Léon Bernard, 35043 Rennes cedex,
France.
Most current anticancer therapies induce tumor cell death through the induction of apoptosis.
However, the biochemical lesions leading to cell death are not always understood. The plasma
membrane has been considered as the most important target, other than DNA, for many
anticancer drugs. From a structural viewpoint, the plasma membrane is an heterogeneous
structure composed of distinct microdomains termed lipid rafts. These lipid rafts are enriched
in cholesterol and sphingolipids (sphingomyelin and glycosphingolipids) thus defining more
ordered area in the plasma membrane. These lipid microdomains actively participate in
several signaling transduction pathways, particularly in the Fas death receptor pathway, and
also in drug-induced apoptosis. We have recently shown that an early and transient increase in
plasma membrane fluidity, determined by a spin-labeling method using EPR (Electron
Paramagnetic Resonance), has been associated to agregation and relocalisation of Fas receptor
into plasma membrane lipid rafts during cisplatin-induced apoptosis in HT29 human colon
cancer cells (Lacour et al., Cancer Res. 2004, 64 (10): 3593-3598).
In order to study the role of plasma membrane fluidity, the effects of membrane stabilizing
agents (ursodeoxycholic acid (UDCA), cholesterol (Chol) and monosyaloganglioside 1
(GM1)) have been investigated in cisplatin-induced apoptosis in HT29 cells.
UDCA, Chol and GM1 inhibit the early increase in plasma membrane fluidity following
cisplatin treatment, and about 30 % the apoptosis induced by cisplatin, without modifying the
entry of cisplatin into HT29 cells (measured by atomic absorption spectrometry). Moreover,
we show that a pretreatment with stabilizing agents inhibits Fas agregation as well as lipid
rafts agregation evidenced by a FITC-cholera toxin labeling on the cell surface of HT29 cells
treated with cisplatin. Altogether, these data suggest that the transient increase in plasma
membrane fluidity contribute to cisplatin-induced early plasma membrane events and
subsequently to cisplatin-induced apoptosis.
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