Altered
cellular metabolism is one of the crucial hallmarks of
glioma that deserves exploration, as the metabolites act as direct
indicators of protein function and genetic variations. The current
study focused on the metabolomic profiling of patients from whom glioma
specimens were obtained for the identification of specific metabolites
that could distinguish the low grade and high grade. In the current
study, 1H NMR spectroscopy was carried out and the data
were analyzed by partial least-squares discriminant analysis (PLS-DA)
and orthogonal projection to latent structure with discriminant analysis
(OPLS-DA). Pathway analysis was done to associate characteristic metabolites
with the grades of sample using MetaboAnalyst 4.0 software based on
the KEGG metabolic pathways database. Distinctive metabolic profiles
among low- and high-grade gliomas with top 15 characteristic metabolites
that could discriminate these grades were identified on the basis
of their VIP scores from the OPLS-DA model. The major altered metabolic
pathways include choline, taurine and hypotaurine, glutamate/glutamine,
glutathione, and phenyl alanine/tyrosine, which were found to be consistent
with the particular grade of a sample. Our study clearly demonstrated
a characteristic metabolic profile of individual grades of glioma,
suggesting that an altered metabolism is consistent with the specific
grades of glioma appreciation and could lead to the development novel
treatment strategies.
Background: Glioma, the most common form of a malignant brain tumour is characterised by a poor prognosis, which is attributable to its resistance against current therapeutic approaches. Temozolomide (TMZ), a DNA alkylating agent, is the first-line drug for glioma treatment. Long-term treatment using TMZ was reported to culminate in the development of resistance with overexpression of multidrug resistance 1 gene coded protein P-glycoprotein, which in turn releases the drugs from the tumour cells. Purpose: Thus, to circumvent such resistance issues, the current study attempted to explore the effect of naringenin (a flavanone) with proven antiglial tumour potential, in mitigating the features of TMZ resistance. Methods: Colony-forming assay, invasion assay and scratch wound assay were performed among the groups, namely tumour control (C6), vehicle control (V), naringenin (NGEN)-treated, drug-resistant tumour cells (C6R), and drug resistance cells added with NGEN (C6R+NGEN), to examine the impact of NGEN on migration and invasion. The effect of NGEN on filopodia length and density during cell migration was also studied in addition to the matrix metalloproteinases (MMP-2 and MMP-9) and p-ERK levels. Results and Conclusion: NGEN and C6R+NGEN groups had shown significant reduction ( P < .01) in length and density of filopodia, colony formation, invasion and wound healing. Further, NGEN could also modify the assessed protein levels ( P < .001), which were involved in migration and invasion in sensitive and resistant cells. Our study had provided the first evidence on NGEN-induced enhanced sensitivity against TMZ resistance with profound influence as an antimigratory and anti-invasive agent.
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