Title: Decreased sensitivity of metastatic cutaneous squamous cell carcinoma cells to the caspase-dependent cell death induced by the flavonoid luteolin is able due to the induction of autopahgy
Authors: Verschooten, Lien
van Kelst, Sofie
Proby, Charlotte
Barrette, Kathleen
Agostinis, Patrizia
Garmyn, Maria #
Issue Date: Jan-2012
Conference: Cell death in cancer location:Amsterdam date:26-28 January 2012
Article number: 57
Abstract: Botanical polyphenols, mainly flavonoids, are widely proposed as very interesting compounds with
possible chemopreventive and therapeutic capacities.
In this study, we showed that in vitro treatment with the flavonoid Luteolin induced caspase
dependent cell death in a model of human cutaneous squamous cell carcinoma (SCC) derived cells,
representing a primary tumor and its metastase. Notably, no cytotoxic effects were observed when
normal human keratinocyte cells were treated with similar LUT doses. Sensitivity to cell death after
Luteolin treatment, was accompanied by inhibition of AKT signaling, and decreased with tumor
progression, as the primary MET1 SCC cells were considerably more sensitive to Luteolin then the
isogenic metastatic MET4 cells. In Luteolin-treated MET4 cells extensive intracellular vacuolization
was observed and characterized as acidic lysosomal vacuoles using acridine orange staining and
LAMP-1 immunofluorescence, suggesting the involvement of autophagy. Using electron microscopy;
mRFP-GFP-LC3 transfection and the autophagy marker p62 protein degradation, we confirmed that
Luteolin increased the autophagic process (increased autolysosome formation and thus enhanced
autophagic flux) in the metastatic MET4 cells. Block of late autophagy using the lysosomotropic agent
chloroquine magnified Luteolin-induced apoptosis in the metastatic SCC cells.
Together, these results suggest that Luteolin exerts the capacity to induce apoptotic cell death in
primary cutaneous SCC and also in more advanced SCC when it is combined with an inhibitor of
autophagosomal degradation. Hence, Luteolin might be a promising agent for the treatment of
cutaneous SCC.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory of Dermatology
Laboratory of Cell Death Research & Therapy
# (joint) last author

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