American Association for Cancer Research
15357163mct160807-sup-175281_3_supp_4171522_mtgq6m.pdf (201.79 kB)

Supplemental Figure 3 from Arginine Deprivation Therapy: Putative Strategy to Eradicate Glioblastoma Cells by Radiosensitization

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journal contribution
posted on 2023-04-03, 15:05 authored by C. Noreen Hinrichs, Mirjam Ingargiola, Theresa Käubler, Steffen Löck, Achim Temme, Alvaro Köhn-Luque, Andreas Deutsch, Olena Vovk, Oleh Stasyk, Leoni A. Kunz-Schughart

Suppl. Figs. 3A-C document some basic findings in the glioblastoma cell line spheroids used in the present study such as ASS/ASL expression and 3-D growth behavior.


European Social Fund

Free State of Saxony

Else Kröner-Fresenius Foundation



Tumor cells—even if nonauxotrophic—are often highly sensitive to arginine deficiency. We hypothesized that arginine deprivation therapy (ADT) if combined with irradiation could be a new treatment strategy for glioblastoma (GBM) patients because systemic ADT is independent of local penetration and diffusion limitations. A proof-of-principle in vitro study was performed with ADT being mimicked by application of recombinant human arginase or arginine-free diets. ADT inhibited two-dimensional (2-D) growth and cell-cycle progression, and reduced growth recovery after completion of treatment in four different GBM cell line models. Cells were less susceptible to ADT alone in the presence of citrulline and in a three-dimensional (3-D) environment. Migration and 3-D invasion were not unfavorably affected. However, ADT caused a significant radiosensitization that was more pronounced in a GBM cell model with p53 loss of function as compared with its p53-wildtype counterpart. The synergistic effect was independent of basic and induced argininosuccinate synthase or argininosuccinate lyase protein expression and not abrogated by the presence of citrulline. The radiosensitizing potential was maintained or even more distinguishable in a 3-D environment as verified in p53-knockdown and p53-wildtype U87-MG cells via a 60-day spheroid control probability assay. Although the underlying mechanism is still ambiguous, the observation of ADT-induced radiosensitization is of great clinical interest, in particular for patients with GBM showing high radioresistance and/or p53 loss of function. Mol Cancer Ther; 17(2); 393–406. ©2017 AACR.See all articles in this MCT Focus section, “Developmental Therapeutics in Radiation Oncology.”