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Title: Sequential treatment by ionizing radiation and sodium arsenite dramatically accelerates TRAIL-mediated apoptosis of human melanoma cells.

Authors: Ivanov, Vladimir N; Zhou, Hongning; Hei, Tom K

Published In Cancer Res, (2007 Jun 1)

Abstract: Melanoma is the most lethal form of skin cancer. There is a lack of effective treatments for individuals with advanced disease. Many melanomas exhibit high levels of radioresistance. The direct consequence of gamma-irradiation for most melanoma cells is growth arrest at the G2-M phase of cell cycle. However, radiation-induced signaling pathways may affect numerous additional targets in cancer cells. We show in the present study that gamma-irradiation, as well as alpha-particle exposure, dramatically increases the susceptibility of melanoma cells to recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis via up-regulation of surface TRAIL-receptor 1/receptor 2 (DR4/DR5) levels and to Fas ligand-mediated apoptosis via up-regulation of surface Fas levels. Additionally, increased dynamin-2 expression after irradiation is critically important in the translocation of death receptor to the cell surface. Moreover, sodium arsenite treatment may up-regulate expression of endogenous TRAIL and induces its translocation to cell surface and further down-regulates cFLIP levels in melanoma cells. We have evaluated the effects of sequential gamma-irradiation and arsenite treatment of melanoma cells for the induction of death signaling. Such treatment results in an efficient TRAIL-mediated apoptosis via a paracrine mechanism. These data highlight the efficacy of combined modality treatment involving radiation and arsenite in clinical management of this often fatal form of skin cancer.

PubMed ID: 17545621 Exiting the NIEHS site

MeSH Terms: Alpha Particles; Antineoplastic Combined Chemotherapy Protocols/pharmacology*; Apoptosis/drug effects; Apoptosis/radiation effects; Arsenites/administration & dosage; Arsenites/pharmacology*; CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism; Combined Modality Therapy; Cycloheximide/pharmacology; Drug Synergism; Dynamin II/biosynthesis; Dynamin II/metabolism; Fas Ligand Protein/biosynthesis; Fas Ligand Protein/metabolism; Gamma Rays; Humans; Melanoma/drug therapy*; Melanoma/pathology; Melanoma/radiotherapy*; Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism; Receptors, Tumor Necrosis Factor/biosynthesis; Receptors, Tumor Necrosis Factor/metabolism; Signal Transduction; Skin Neoplasms/drug therapy*; Skin Neoplasms/pathology; Skin Neoplasms/radiotherapy*; Sodium Compounds/administration & dosage; Sodium Compounds/pharmacology*; TNF-Related Apoptosis-Inducing Ligand/administration & dosage; TNF-Related Apoptosis-Inducing Ligand/pharmacology*

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