Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells
Нема приказа
Аутори
Lefranc, FlorenceMijatovic, Tatjana
Kondo, Yasuko
Sauvage, Sebastien
Roland, Isabelle
Debeir, Olivier
Krstić, Danijela Z.
Vasić, Vesna M.
Gailly, Philippe
Kondo, Seiji
Blanco, Gustavo
Kiss, Robert
Чланак у часопису
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OBJECTIVE: Ion transporters play pivotal roles in cancer cell migration in general and in glioblastomas (GBMs) in particular. However, the specific role of Na+/K+-ATPase (the sodium pump) and, in particular, its alpha 1 subunit, has remained unexplored in GBMs. MATERIALS AND METHODS: The expression of Na+/K+-ATPase alpha 1 in GBM clinical samples, normal brain tissue, and a human GBM cell line has been investigated. Using the novel cardenolide UNBS1450 (Unibioscreen, Brussels, Belgium), which is a ligand of the sodium pump, we have characterized the effects of inhibiting Na+/K+-ATPase alpha 1 in human GBM cells with respect to cell proliferation; morphology; impact on intracellular Na+, Ca2+, and adenosine triphosphate; and changes in the actin cytoskeleton. We have investigated the mechanism by which UNBS1450 overcomes the apoptosis resistance of GBMs and determined its anti-tumor effects in comparative studies in vitro in GBM cell viability assays and in vivo using an orthotopic huma...n GBM xenograft model. RESULTS: Overall, the alpha 1 subunit of Na+/K+-ATPase is highly expressed in a majority of glioblastomas compared with normal brain tissues, and by binding to this subunit in human U373-MG GBM cells, UNBS1450 impairs cell proliferation and migration via an intracellular adenosine triphosphate decrease-mediated disorganization of the actin cytoskeleton and cytotoxic proautophagic effects. UNBS1450 also significantly increases the in vivo survival of mice orthotopically grafted with U373-MG GBM cells. CONCLUSION: Inhibition of the Na+/K+-ATPase alpha 1 subunit in human GBM cells impairs both cell migration and cell proliferation.
Кључне речи:
autophagy / glioblastoma / migration / orthotopic xenografts / sodium pump / temozolomideИзвор:
Neurosurgery, 2008, 62, 1, 211-221
DOI: 10.1227/01.NEU.0000296985.39041.52
ISSN: 0148-396X
PubMed: 18300910
WoS: 000252978100044
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Институција/група
VinčaTY - JOUR AU - Lefranc, Florence AU - Mijatovic, Tatjana AU - Kondo, Yasuko AU - Sauvage, Sebastien AU - Roland, Isabelle AU - Debeir, Olivier AU - Krstić, Danijela Z. AU - Vasić, Vesna M. AU - Gailly, Philippe AU - Kondo, Seiji AU - Blanco, Gustavo AU - Kiss, Robert PY - 2008 UR - https://vinar.vin.bg.ac.rs/handle/123456789/3358 AB - OBJECTIVE: Ion transporters play pivotal roles in cancer cell migration in general and in glioblastomas (GBMs) in particular. However, the specific role of Na+/K+-ATPase (the sodium pump) and, in particular, its alpha 1 subunit, has remained unexplored in GBMs. MATERIALS AND METHODS: The expression of Na+/K+-ATPase alpha 1 in GBM clinical samples, normal brain tissue, and a human GBM cell line has been investigated. Using the novel cardenolide UNBS1450 (Unibioscreen, Brussels, Belgium), which is a ligand of the sodium pump, we have characterized the effects of inhibiting Na+/K+-ATPase alpha 1 in human GBM cells with respect to cell proliferation; morphology; impact on intracellular Na+, Ca2+, and adenosine triphosphate; and changes in the actin cytoskeleton. We have investigated the mechanism by which UNBS1450 overcomes the apoptosis resistance of GBMs and determined its anti-tumor effects in comparative studies in vitro in GBM cell viability assays and in vivo using an orthotopic human GBM xenograft model. RESULTS: Overall, the alpha 1 subunit of Na+/K+-ATPase is highly expressed in a majority of glioblastomas compared with normal brain tissues, and by binding to this subunit in human U373-MG GBM cells, UNBS1450 impairs cell proliferation and migration via an intracellular adenosine triphosphate decrease-mediated disorganization of the actin cytoskeleton and cytotoxic proautophagic effects. UNBS1450 also significantly increases the in vivo survival of mice orthotopically grafted with U373-MG GBM cells. CONCLUSION: Inhibition of the Na+/K+-ATPase alpha 1 subunit in human GBM cells impairs both cell migration and cell proliferation. T2 - Neurosurgery T1 - Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells VL - 62 IS - 1 SP - 211 EP - 221 DO - 10.1227/01.NEU.0000296985.39041.52 ER -
@article{ author = "Lefranc, Florence and Mijatovic, Tatjana and Kondo, Yasuko and Sauvage, Sebastien and Roland, Isabelle and Debeir, Olivier and Krstić, Danijela Z. and Vasić, Vesna M. and Gailly, Philippe and Kondo, Seiji and Blanco, Gustavo and Kiss, Robert", year = "2008", abstract = "OBJECTIVE: Ion transporters play pivotal roles in cancer cell migration in general and in glioblastomas (GBMs) in particular. However, the specific role of Na+/K+-ATPase (the sodium pump) and, in particular, its alpha 1 subunit, has remained unexplored in GBMs. MATERIALS AND METHODS: The expression of Na+/K+-ATPase alpha 1 in GBM clinical samples, normal brain tissue, and a human GBM cell line has been investigated. Using the novel cardenolide UNBS1450 (Unibioscreen, Brussels, Belgium), which is a ligand of the sodium pump, we have characterized the effects of inhibiting Na+/K+-ATPase alpha 1 in human GBM cells with respect to cell proliferation; morphology; impact on intracellular Na+, Ca2+, and adenosine triphosphate; and changes in the actin cytoskeleton. We have investigated the mechanism by which UNBS1450 overcomes the apoptosis resistance of GBMs and determined its anti-tumor effects in comparative studies in vitro in GBM cell viability assays and in vivo using an orthotopic human GBM xenograft model. RESULTS: Overall, the alpha 1 subunit of Na+/K+-ATPase is highly expressed in a majority of glioblastomas compared with normal brain tissues, and by binding to this subunit in human U373-MG GBM cells, UNBS1450 impairs cell proliferation and migration via an intracellular adenosine triphosphate decrease-mediated disorganization of the actin cytoskeleton and cytotoxic proautophagic effects. UNBS1450 also significantly increases the in vivo survival of mice orthotopically grafted with U373-MG GBM cells. CONCLUSION: Inhibition of the Na+/K+-ATPase alpha 1 subunit in human GBM cells impairs both cell migration and cell proliferation.", journal = "Neurosurgery", title = "Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells", volume = "62", number = "1", pages = "211-221", doi = "10.1227/01.NEU.0000296985.39041.52" }
Lefranc, F., Mijatovic, T., Kondo, Y., Sauvage, S., Roland, I., Debeir, O., Krstić, D. Z., Vasić, V. M., Gailly, P., Kondo, S., Blanco, G.,& Kiss, R.. (2008). Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells. in Neurosurgery, 62(1), 211-221. https://doi.org/10.1227/01.NEU.0000296985.39041.52
Lefranc F, Mijatovic T, Kondo Y, Sauvage S, Roland I, Debeir O, Krstić DZ, Vasić VM, Gailly P, Kondo S, Blanco G, Kiss R. Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells. in Neurosurgery. 2008;62(1):211-221. doi:10.1227/01.NEU.0000296985.39041.52 .
Lefranc, Florence, Mijatovic, Tatjana, Kondo, Yasuko, Sauvage, Sebastien, Roland, Isabelle, Debeir, Olivier, Krstić, Danijela Z., Vasić, Vesna M., Gailly, Philippe, Kondo, Seiji, Blanco, Gustavo, Kiss, Robert, "Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells" in Neurosurgery, 62, no. 1 (2008):211-221, https://doi.org/10.1227/01.NEU.0000296985.39041.52 . .