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Planta Med 2016; 82(18): 1532-1539
DOI: 10.1055/s-0042-114780
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

α-Hederin Induces Apoptosis, Membrane Permeabilization and Morphologic Changes in Two Cancer Cell Lines Through a Cholesterol-Dependent Mechanism

Joseph H. Lorent
1   Université catholique de Louvain, Louvain Drug Research Institute, Cellular and Molecular Pharmacology, Bruxelles, Belgium
2   Université catholique de Louvain, Louvain Drug Research Institute, Pharmacognosy, Bruxelles, Belgium
,
Catherine Léonard
1   Université catholique de Louvain, Louvain Drug Research Institute, Cellular and Molecular Pharmacology, Bruxelles, Belgium
,
Marthe Abouzi
1   Université catholique de Louvain, Louvain Drug Research Institute, Cellular and Molecular Pharmacology, Bruxelles, Belgium
,
Farida Akabi
1   Université catholique de Louvain, Louvain Drug Research Institute, Cellular and Molecular Pharmacology, Bruxelles, Belgium
,
Joëlle Quetin-Leclercq
2   Université catholique de Louvain, Louvain Drug Research Institute, Pharmacognosy, Bruxelles, Belgium
,
Marie-Paule Mingeot-Leclercq
1   Université catholique de Louvain, Louvain Drug Research Institute, Cellular and Molecular Pharmacology, Bruxelles, Belgium
› Author Affiliations
Further Information

Publication History

received 18 March 2016
revised 21 July 2016

accepted 04 August 2016

Publication Date:
30 August 2016 (online)

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Abstract

In perspective of reducing the mortality of cancer, there is a high interest in compounds which act on multiple cellular targets and therefore prevent the appearance of cancer resistances. Saponins and α-hederin, an oleanane-type saponin, induce cancer cell death through different pathways, including apoptosis and membrane permeabilization. Unfortunately, the mechanism by which cell death is induced is unknown. We hypothesized that the activity of α-hederin mainly depends on its interaction with membrane cholesterol and therefore investigated the cholesterol and saponin-structure dependency of apoptosis and membrane permeabilization in two malignant monocytic cell lines. Apoptotic cell death and membrane permeabilization were significantly reduced in cholesterol-depleted cells. Permeabilization further depended upon the osidic side chain of α-hederin and led to extracellular calcium influx and nuclear fragmentation, with only the latter being susceptible to caspase inhibitors. Membrane order, measured by laurdan generalized polarization imaging, was neither reduced by α-hederin nor its aglycone hederagenin suggesting that their activity was not related to membrane cholesterol extraction. However, a radical change in morphology, including the disappearance of pseudopodes was observed upon incubation with α-hederin. Our results suggest that the different activities of α-hederin mainly depend on its interaction with membrane cholesterol and consequent pore formation.

Key words

saponin - triterpenic acid - apoptosis - membrane permeabilization - cholesterol

Supporting Information

 

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