Arginine deprivation by arginine deiminase of Streptococcus pyogenes controls primary glioblastoma growth in vitro and in vivo

Cancer Biology & Therapy
Tomas FiedlerClaudia Maletzki

Abstract

Arginine auxotrophy constitutes a weak point of several tumors, among them glioblastoma multiforme (GBM). Hence, those tumors are supposed to be sensitive for arginine-depleting substances, such as arginine deiminase (ADI). Here we elucidated the sensitivity of patient-individual GBM cell lines toward Streptococcus pyogenes-derived ADI. To improve therapy, ADI was combined with currently established and pre-clinical cytostatic drugs. Additionally, effectiveness of local ADI therapy was determined in xenopatients. Half of the GBM cell lines tested responded well toward ADI monotherapy. In those cell lines, viability decreased significantly (up to 50%). Responding cell lines were subjected to combination therapy experiments to test if any additive or even synergistic effects may be achieved. Such promising results were obtained in 2/3 cases. In cell lines HROG02, HROG05 and HROG10, ADI and Palomid 529 combinations were most effective yielding more than 70% killing after 2 rounds of treatment. Comparable boosted antitumoral effects were observed after adding chloroquine to ADI (>60% killing). Apoptosis, as well as cell cycle dysregulation were found to play a minor role. In some, but clearly not all cases, (epi-) genetic silencing...Continue Reading

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Citations

Dec 24, 2015·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Eleonora A StarikovaVadim B Vasilyev
Jul 29, 2017·Journal of Hematology & Oncology·Marcus Kwong Lam Fung, Godfrey Chi-Fung Chan
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Methods Mentioned

BETA
xenograft
flow cytometry
PCR
xenografts
Assay
FCS

Software Mentioned

Plot
Sigma

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