Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation

Wells, James W., Evans, Christopher H., Scott, Milcah C., Ruetgen, Barbara C., O'Brien, Timothy D., Modiano, Jaime F., Cvetkovic, Goran and Tepic, Slobodan (2013) Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation. PLoS One, 8 1: e54464.1-e54464.9. doi:10.1371/journal.pone.0054464


Author Wells, James W.
Evans, Christopher H.
Scott, Milcah C.
Ruetgen, Barbara C.
O'Brien, Timothy D.
Modiano, Jaime F.
Cvetkovic, Goran
Tepic, Slobodan
Title Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-01
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0054464
Open Access Status DOI
Volume 8
Issue 1
Start page e54464.1
End page e54464.9
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.
Keyword Acute Lymphoblastic Leukemias
Recombinant Human Arginase
L Asparaginase Therapy
Amino Acid
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 08 May 2013, 11:51:25 EST by Dr James Wells on behalf of UQ Diamantina Institute