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Title: Phenalenone-photodynamic therapy induces apoptosis on human tumor cells mediated by caspase-8 and p38-MAPK activation
Authors: Salmerón, María L.
Quintana-Aguiar, Jose 
De la Rosa, Juan V. 
Lopez-Blanco, Felix 
Castrillo, Antonio 
Gallardo, German 
Tabraue, Carlos 
UNESCO Clasification: 32 Ciencias médicas
Keywords: Apoptosis
Photodynamic therapy
Tumor cell
Issue Date: 2018
Publisher: 0899-1987
Project: Control de la Respuesta Inmuno-Inflamatoria en El Pulmón Por Receptores Nucleares Lxr 
Journal: Molecular Carcinogenesis 
Abstract: Photodynamic therapy (PDT) is a rising and hopeful treatment for solid tumors and others malignancies. PDT uses harmless visible light to activate a tumor-associated photosensitizer (PS). The excited PS generates cytotoxic reactive oxygen species (ROS) that induce damage and death of tumor cells. It is known that certain phytoalexins and phytoanticipins derived from plants often display a PS-like activity due to a phenalenone (PN) moietyan efficient singlet oxygen photosensitizerin its skeleton. The aim of this study is to explore the phototoxic properties of PN on the human cell line tumor-derived HL60 (acute promyelocytic leukemia) and to identify the cell-specific targets of ROS involved in the tumor cell death. Our results reveal that PN acts as an excellent PS, showing a potent antitumor cell activity in presence of light. PN-PDT generates intracellular ROS, via oxidation reaction mechanisms type I and II, resulting in an induction of apoptosis. Moreover, both extrinsic (through direct activation of caspase-3) and intrinsic (through mitochondrial depolarization) pathways of apoptosis are induced by PN-PDT. Using pharmacologic inhibitors, we also find that PN-PDT activates caspase-8/tBid and p38-MAPK, triggering the activation of the apoptotic pathways. Although, survival pathways are also promoted through PI3K/Akt and JNK activation, the net result of PN-PDT is the tumor cell death. The present work identifies to PN, for the first time, as a potent photosensitizer in human tumor cell lines and proposes a mechanism by which ROS induces apoptosis of tumor cell.
ISSN: 0899-1987
DOI: 10.1002/mc.22875
Source: Molecular Carcinogenesis [ISSN 0899-1987], v. 57 (11), p. 1525-1539
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