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Mitochondrial perturbation, oxidative stress and lysosomal destabilization are involved in 7β-hydroxysitosterol and 7β-hydroxycholesterol triggered apoptosis in human colon cancer cells

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Abstract

We reported previously that 7β-hydroxysitosterol and 7β-hydroxycholesterol induced apoptosis in Caco-2 cells. Apoptosis caused by 7β-hydroxysitosterol but not by 7β-hydroxycholesterol was related to a caspase-dependent process. In the present report, we compared the effects of both compounds on mitochondria integrity and on various modulators of apoptosis. When Caco-2 cells were exposed to both hydroxysterols, no changes in Bcl-2 and Bax expressions were detected indicating a Bcl-2/Bax-independent cell death pathway, whereas loss of mitochondrial membrane potential and cytochrome c release were observed. Endonuclease G expression and enhanced production of reactive oxygen species were detected in 7β-hydroxycholesterol treated cells, but not with 7β-hydroxysitosterol. Loss of mitochondrial membrane potential and cell death produced by both hydroxysterols were prevented by vitamin C. Lysosomal membrane integrity was altered with both hydroxysterols, but 7β-hydroxysitosterol was significantly more active on than 7β-hydroxycholesterol. Both hydroxysterols induced apoptosis by mitochondrial membrane permeabilization. However, 7β-hydroxycholesterol exhibited a specific enhancement of oxidative stress and of endonuclease G expression despite its closely related chemical structure with 7β-hydroxysitosterol. The two hydroxysterols exhibit different lipophilic properties which may explain their different biological effects.

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Authors and Affiliations

  1. INSERM U682, Université Louis Pasteur EA3430, IRCAD, 1, place de l’Hôpital, BP406, 67091, Strasbourg-Cedex, France

    Stamatiki Roussi, Francine Gossé & Francis Raul

  2. Aérial, 19 rue de Saint Junien, 67300, Schiltigheim, France

    Dalal Aoudé-Werner

  3. Laboratoire de Chimie Analytique et Sciences de l’Aliment, ULP/CNRS UMR 7512, Faculté de pharmacie, 74, route du Rhin, 67400, Illkirch, France

    Xin Zhang & Eric Marchioni

  4. Laboratoire de Chimie Organique Synthétique, ULP/CNRS UMR 7123, 1, rue Blaise Pascal, 67008, Strasbourg-Cedex, France

    Philippe Geoffroy & Michel Miesch

  5. Laboratory of Nutritional Cancer Prevention, IRCAD, 1, Place de l’Hôpital, 67091, Strasbourg, France

    Stamatiki Roussi

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  1. Stamatiki Roussi
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Correspondence to Stamatiki Roussi.

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Roussi, S., Gossé, F., Aoudé-Werner, D. et al. Mitochondrial perturbation, oxidative stress and lysosomal destabilization are involved in 7β-hydroxysitosterol and 7β-hydroxycholesterol triggered apoptosis in human colon cancer cells. Apoptosis 12, 87–96 (2007). https://doi.org/10.1007/s10495-006-0485-y

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