Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 84
APOPTOTIC PROPERTIES OF HYPERFORIN ON HUMAN B-CLL LEUKEMIC
CELLS
Claire Quiney, Christian Billard, Pezhman Mirshahi, Anne-Marie Faussat, Jean-
Dominique Fourneron *, and Jean-Pierre Kolb.
INSERM U736, Centre Biomédical des Cordeliers, Paris and * UMR6171, Faculté des
Sciences St Jérôme, Marseille
The natural compound hyperforin (HF), purified from Saint John’s wort, was tested on
leukemic cells from B cell lymphocytic leukemia (B-CLL) patients and on the ESKOL cell
line derived from a patient with hairy cell leukemia. HF was found to inhibit the proliferation
of ESKOL cells (IC50 around 1 µg/ml) and to elicit their apoptosis. Similarly, HF triggered a
time- and dose-dependent induction of apoptosis in B-CLL leukemic cells that was detected
by the increase in the percentage of annexinV-labelled cells and the augmentation of
internucleosomal DNA fragmentation. This was accompanied by the activation of caspase 3,
the disruption of the mitochondrial transmembrane potential &*m and the inhibition of nitric
oxide (NO) production. HF-induced apoptosis was reverted in the presence of the general
caspases inhibitor Z-VAD-fmk.
Incubation of B-CLL cells with HF also resulted in a marked suppression of their capacity to
release matrix metalloprotease 9 (MMP-9), an essential component in the degradation of the
extra cellular matrix. In addition, HF prevented the formation of tubules by human bone
marrow endothelial cells (HBMEC) cultured on matrigel, emphasizing its potential interest as
an anti neo-vasculogenesis drug.
Moreover, HF was found to impair the activity of several ABC pumps that are involved in the
multidrug resistance of the leukemic cells against chemotherapeutic reagents.
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