autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells自噬抑制剂氯喹增强的细胞死亡诱导影响类黄酮木樨草素在转移性鳞状细胞癌的细胞.pdf

Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells 1 1 1 ´ 2 3 Lien Verschooten , Kathleen Barrette , Sofie Van Kelst , Noemı Rubio Romero , Charlotte Proby , Rita De 4 2 1 Vos , Patrizia Agostinis , Marjan Garmyn * 1 Dermatology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium, 2 Cellular and Molecular Medicine, Laboratory for Cell Death and Therapy, KU Leuven, Leuven, Belgium, 3 Cancer Research UK Cancer Centre Dundee, College of Medicine, Dentistry and Nursing, University of Dundee, Dundee, Scotland, 4 Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium Abstract Background: Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities. Methods Results: 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 matched pair of primary tumor and its metastasis. Notably, no cytotoxic effects were observed in normal human keratinocytes when treated with similar doses of Luteolin. Luteolin-induced apoptosis was accompanied by inhibition of AKT signaling, and sensitivity decreased with tumor progression, as the primary MET1 SCC cells were considerably more sensitive to Luteolin than the isogenic metastatic MET4 cells. Extensive intracellular vacuolization was observed in Luteolin-treated MET4 cells, which were characterized as acidic lysosomal vacuoles