1. Planta Med. 2016 Dec;82(18):1532-1539. Epub 2016 Aug 30.

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

Lorent JH(1), Léonard C(1), Abouzi M(1), Akabi F(1), Quetin-Leclercq J(2),
Mingeot-Leclercq MP(1).

Author information: 
(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.

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

Georg Thieme Verlag KG Stuttgart · New York.

DOI: 10.1055/s-0042-114780 
PMID: 27574896  [PubMed - in process]