Live-Cell Synchrotron-Based FTIR Evaluation of Metabolic Compounds in Brain Glioblastoma Cell Lines after Riluzole Treatment

Abstract

Glioblastoma multiforme (GBM) is the most aggressive brain tumor, characterized by short median survival and an almost 100% tumor-related mortality. The standard of care treatment for newly diagnosed GBM includes surgical resection followed by concomitant radiochemotherapy. The prevention of disease progression fails due to the poor therapeutic effect caused by the great molecular heterogeneity of this tumor. Previously, we exploited synchrotron radiation-based soft X-ray tomography and hard X-ray fluorescence for elemental microimaging of the shock-frozen GBM cells. The present study focuses instead on the biochemical profiling of live GBM cells and provides new insight into tumor heterogenicity. We studied bio-macromolecular changes by exploring the live-cell synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy in a set of three GBM cell lines, including the patient-derived glioblastoma cell line, before and after riluzole treatment, a medicament with potential anticancer properties. SR-FTIR microspectroscopy shows that GBM live cells of different origins recruit different organic compounds. The riluzole treatment of all GBM cell lines mainly affected carbohydrate metabolism and the DNA structure. Lipid structures and protein secondary conformation are affected as well by the riluzole treatment: cellular proteins assumed cross β-sheet conformation while parallel β-sheet conformation was less represented for all GBM cells. Moreover, we hope that a new live-cell approach for GBM simultaneous treatment and examination can be devised to target cancer cells more specifically, i.e., future therapies can develop more specific treatments according to the specific bio-macromolecular signature of each tumor type.

potencial uso do riluzole no tratamento do câncer

“…Nesta revisão foi constatado que o riluzole está sendo especialmente utilizado para tratamentos de melanomas 17,25,32,52,59 , gliomas 13,16,84 , neuroblastomas 5,18,27 , tumores de mama 7,31,33,43,61 e próstata 26,89,90 , inibindo o crescimento de células cancerígenas e induzindo a apoptose. As pesquisas acompanharam o perfil epidemiológico mundial da incidência e mortalidade por câncer, exceto os cânceres de pulmão.…”

“…O riluzole afetou principalmente o metabolismo de carboidratos e a estrutura do DNA. As estruturas lipídicas e a conformação secundária da proteína também são afetadas pelo tratamento com riluzole: as proteínas celulares assumiram a conformação em folha β cruzada enquanto a conformação em folha β paralela foi menos representada para todas as células gliobastomas 84 . Em outra pesquisa, o riluzole apresentou efeitos inibidores de crescimento dependentes do tempo e da dose significativos em todas as linhas de células gliobastomas avaliadas independentemente.…”

“…Outro estudo com melanoma demonstrou que o riluzole induz o aumento da fosforilação de ligação smad, do lançamento de inibição do glutamato desencadeando seu acúmulo intracelular e inibindo o crescimento das células do tumor no espaço intersticial 35 . Em 2021, pesquisas apontam que o riluzole foi escolhido como potencial alvo terapêutico principalmente no controle imunológico contra câncer de mama e glioblastoma 84,85,87,88 .…”

Advanced Waveguide Based LOC Biosensors: A Minireview

“…In this regard, a research group [ 75 ] studied and employed synchrotron FT-IR to study the chemical reactions of astrocytes connected to gene variants of the oxidoreductase enzyme copper, zinc superoxide dismutase, involved in familial amyotrophic lateral sclerosis (ALS), and accounting for 5 to 10% of all ALS cases, and which is a progressive neurodegenerative disease that results in muscle weakness, disability, and, finally, death Figure 2 .…”

“…These researchers employed (SR-FTIR) to comprehend the biochemical changes in motor neuron disorder and established a confined intensification of ν s/as (CH 2 ), ν s/as (CH 3 ), and ν(C=O) bond vibrations and explained the higher accumulation of phospholipids in the middle area of ALS astrocytes and the substantial phospholipid acyl concentration, which were absent in nontransgenic littermate (Ngs) model astrocytes [ 75 , 77 , 78 ]. The above-mentioned spectroscopic impression permitted distinguishing the immense accumulation of phospholipid vesicles and superoxide dismutase 1 enzyme, oxidative degradation of lipids, and metabolic choline regulations; these allowed subsequent biomarker location and the evolution of unique diagnostic policies.…”