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2015 ; 5
(ä): 15556
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Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem
cell differentiation and death
#MMPMID26494310
Daniele S
; Giacomelli C
; Zappelli E
; Granchi C
; Trincavelli ML
; Minutolo F
; Martini C
Sci Rep
2015[Oct]; 5
(ä): 15556
PMID26494310
show ga
Therapies that target the signal transduction and metabolic pathways of cancer
stem cells (CSCs) are innovative strategies to effectively reduce the recurrence
and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs
exhibit an increased rate of glycolysis, thus rendering them intrinsically more
sensitive to prospective therapeutic strategies based on the inhibition of the
glycolytic pathway. The enzyme lactate dehydrogenase-A (LDH-A), which catalyses
the interconversion of pyruvate and lactate, is up-regulated in human cancers,
including GBM. Although several papers have explored the benefits of targeting
cancer metabolism in GBM, the effects of direct LDH-A inhibition in glial tumours
have not yet been investigated, particularly in the stem cell subpopulation.
Here, two representative LDH-A inhibitors (NHI-1 and NHI-2) were studied in
GBM-derived CSCs and compared to differentiated tumour cells. LDH-A inhibition
was particularly effective in CSCs isolated from different GBM cell lines, where
the two compounds blocked CSC formation and elicited long-lasting effects by
triggering both apoptosis and cellular differentiation. These data demonstrate
that GBM, particularly the stem cell subpopulation, is sensitive to glycolytic
inhibition and shed light on the therapeutic potential of LDH-A inhibitors in
this tumour type.