TY - JOUR
T1 - Live-Cell Synchrotron-Based FTIR Evaluation of Metabolic Compounds in Brain Glioblastoma Cell Lines after Riluzole Treatment
AU - Dučić, Tanja
AU - Ninkovic, Milena
AU - Martínez-Rovira, Immaculada
AU - Sperling, Swetlana
AU - Rohde, Veit
AU - Dimitrijević, Dragoljub
AU - Jover Mañas, Gabriel Vicent
AU - Vaccari, Lisa
AU - Birarda, Giovanni
AU - Yousef, Ibraheem
N1 - Funding Information:
The authors thank the Elettra Synchrotron facility for beamtime allocation (Experiment No. 20185148) and excellent working conditions. The work of T.D. was carried out with financial support from the in-house project 2019–2020 at ALBA Synchrotron and in-house Proposal No. 2020014052. I.M.-R. acknowledges the financial support from the Spanish Ministry of Science, Innovation and Universities (Fellowship RYC2018-024043-I). The authors are thankful to Marta Semrau and Paola Storici from the Structural Biology Laboratory at Elettra Synchrotron for help during cell culturing on the site. Artur Surowka is acknowledged for discussions during beamtime and Carlos Falcon for testing the script for water subtraction.
Publisher Copyright:
© 2021 American Chemical Society
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122670850&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.1c02076
DO - 10.1021/acs.analchem.1c02076
M3 - Article
C2 - 34965097
AN - SCOPUS:85122670850
SN - 0003-2700
VL - 94
SP - 1932
EP - 1940
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 4
ER -
