title: Vitamin E synthetic derivate-TPGS-selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia.
abstract: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of natural vitamin E commonly used as a drug delivery agent. Recently, TPGS alone has been reported to induce cell death in lung, breast and prostate cancer. However, the effect of TPGS on cancer cell viability remains unclear. Thus, this study was aimed to evaluate the cytotoxic effect of TPGS on human periphral blood lymphocytes (PBL) and on T cell acute lymphocytic leukemia (ALL) Jurkat clone E6-1 cells and its possible mechanism of action. PBL and Jurkat cells were treated with TPGS (10, 20, 40, 60, and 80 μM), and morphological changes in the cell nucleus, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species levels were determined by immune-fluorescence microscopy and flow cytometry. Cellular apoptosis markers were also evaluated by immunocytochemistry. In this study, TPGS induced apoptotic cell death in Jurkat cells, but not in PBL, in a dose-response manner with increasing nuclear DNA fragmentation, increasing cell cycle arrest, and decreasing ΔΨm. Additionally, TPGS increased dichlorofluorescein fluorescence intensity, indicative of H2O2 production, in a dose-independent fashion. TPGS increased DJ-1 Cys(106)-sulfonate, as a marker of intracellular stress and induced the activation of NF-κB, p53 and c-Jun transcription factors. Additionally, it increased the expression of apoptotic markers Bcl-2 related pro-apoptotic proteins Bax and PUMAand activated caspase-3. The antioxidant N-acetyl-L-cysteine and known pharmacological inhibitors protected the cells from the TPGS induced effects. In conclusion, TPGS selectively induces apoptosis in Jurkat cells through two independent but complementary H2O2-mediated signaling pathways. Our findings support the use of TPGS as a potential treatment for ALL.
authors.affiliation: Neuroscience Research Group, Faculty of Medicine, Medical Research Institute, University of Antioquia, Calle 70 N° 52-21, and Calle 62 #52-59, Building 1, Room 412, SIU, P. O. Box 1226, Medellín, Colombia.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ruiz-Moreno
authors.affiliation: Neuroscience Research Group, Faculty of Medicine, Medical Research Institute, University of Antioquia, Calle 70 N° 52-21, and Calle 62 #52-59, Building 1, Room 412, SIU, P. O. Box 1226, Medellín, Colombia.
authors.forename: Marlene
authors.initials: M
authors.lastname: Jimenez-Del-Rio
authors.affiliation: Material Science Group, Faculty of Chemistry, University of Antioquia, Calle 70 N° 52-21, and Calle 62 #52-59, Building 1, Room 310, SIU, P. O. Box 1226, Medellin, Colombia.
authors.forename: Ligia
authors.initials: L
authors.lastname: Sierra-Garcia
authors.affiliation: Material Science Group, Faculty of Chemistry, University of Antioquia, Calle 70 N° 52-21, and Calle 62 #52-59, Building 1, Room 310, SIU, P. O. Box 1226, Medellin, Colombia.
authors.forename: Betty
authors.initials: B
authors.lastname: Lopez-Osorio
authors.affiliation: Neuroscience Research Group, Faculty of Medicine, Medical Research Institute, University of Antioquia, Calle 70 N° 52-21, and Calle 62 #52-59, Building 1, Room 412, SIU, P. O. Box 1226, Medellín, Colombia. calberto.velez@udea.edu.co.
authors.forename: Carlos
authors.initials: C
authors.lastname: Velez-Pardo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014810:Vitamin E; C014225:tocophersolan
keywords: Alpha-tocopheryl polyethylene glycol succinate; Apoptosis; Jurkat; Leukemia; Vitamin E