Artículo
Proliferative glioblastoma cancer cells exhibit persisting temporal control of metabolism and display differential temporal drug susceptibility in chemotherapy
Wagner, Paula Micaela
; Sosa Alderete, Lucas Gastón
; Gorne, Lucas Damián
; Gaveglio, Virginia Lucía
; Salvador, Gabriela Alejandra
; Pasquaré, Susana Juana; Guido, Mario Eduardo
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Fecha de publicación:
02/2019
Editorial:
Humana Press
Revista:
Molecular Neurobiology
ISSN:
0893-7648
e-ISSN:
1559-1182
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Even in immortalized cell lines, circadian clocks regulate physiological processes in a time-dependent manner, driving transcriptional and metabolic rhythms, the latter being able to persist without transcription. Circadian rhythm disruptions in modern life (shiftwork, jetlag, etc.) may lead to higher cancer risk. Here, we investigated whether the human glioblastoma T98G cells maintained quiescent or under proliferation keep a functional clock and whether cells display differential time responses to bortezomib chemotherapy. In arrested cultures, mRNAs for clock (Per1, Rev-erbα) and glycerophospholipid (GPL)-synthesizing enzyme genes, 32 P-GPL labeling, and enzyme activities exhibited circadian rhythmicity; oscillations were also found in the redox state/peroxiredoxin oxidation. In proliferating cells, rhythms of gene expression were lost or their periodicity shortened whereas the redox and GPL metabolisms continued to fluctuate with a similar periodicity as under arrest. Cell viability significantly changed over time after bortezomib treatment; however, this rhythmicity and the redox cycles were altered after Bmal1 knock-down, indicating cross-talk between the transcriptional and the metabolic oscillators. An intrinsic metabolic clock continues to function in proliferating cells, controlling diverse metabolisms and highlighting differential states of tumor suitability for more efficient, time-dependent chemotherapy when the redox state is high and GPL metabolism low.
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Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos(IMBIV)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA VEGETAL (P)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA VEGETAL (P)
Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
Wagner, Paula Micaela; Sosa Alderete, Lucas Gastón; Gorne, Lucas Damián; Gaveglio, Virginia Lucía; Salvador, Gabriela Alejandra; et al.; Proliferative glioblastoma cancer cells exhibit persisting temporal control of metabolism and display differential temporal drug susceptibility in chemotherapy; Humana Press; Molecular Neurobiology; 56; 2; 2-2019; 1276-1292
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