PMID- 22546217
OWN - NLM
STAT- MEDLINE
DCOM- 20121220
LR  - 20211203
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 5
DP  - 2012 Apr 30
TI  - Deprivation of arginine by recombinant human arginase in prostate cancer cells.
PG  - 17
LID - 10.1186/1756-8722-5-17 [doi]
AB  - BACKGROUND: Recombinant human arginase (rhArg) has been developed for arginine 
      deprivation therapy in cancer, and is currently under clinical investigation. 
      During pre-clinical evaluation, rhArg has exhibited significant 
      anti-proliferative activity in cancer cells deficient in the expression of 
      ornithine carbamoyl transferase (OCT). Interestingly, a variety of cancer cells 
      such as melanoma and prostate cancer deficient in argininosuccinate synthetase 
      (ASS) are sensitive to arginine deprivation by arginine deiminase. In this study, 
      we investigated levels of gene expression of OCT and ASS, and the effects of 
      rhArg in human prostate cancer cells: LNCaP (androgen-dependent), PC-3 and DU-145 
      (both androgen-independent). RESULTS: Quantitative real-time PCR showed minimal 
      to absent gene expression of OCT, but ample expression of ASS expression in all 3 
      cell lines. Cell viability assay after 72-h exposure of rhArg showed all 3 lines 
      had half maximal inhibitory concentration less than or equal to 0.02 U/ml. 
      Addition of ornithine to cell culture media failed to rescue these cells from 
      rhArg-mediated cytotoxicity.Decreased phosphorylation of 4E-BP1, a downstream 
      effector of mammalian target of rapamycin (mTOR), was noted in DU-145 and PC-3 
      after exposure to rhArg. Moreover, there was no significant apoptosis induction 
      after arginine deprivation by rhArg in all 3 prostate cancer cell lines. 
      CONCLUSION: rhArg causes significant cytotoxicity in LNCaP, DU-145 and PC-3 
      prostate cancer cells which all demonstrate decreased OCT expression. Inhibition 
      of mTOR manifested by hypophosphorylation of 4E-BP1 suggests autophagy is 
      involved as alternative cell death mechanism. rhArg demonstrates a promising 
      novel agent for prostate cancer treatment.
FAU - Hsueh, Eddy C
AU  - Hsueh EC
AD  - Department of Surgery, Saint Louis University, St. Louis, MO, USA.
FAU - Knebel, Stephanie M
AU  - Knebel SM
FAU - Lo, Wai-Hung
AU  - Lo WH
FAU - Leung, Yun-Chung
AU  - Leung YC
FAU - Cheng, Paul Ning-Man
AU  - Cheng PN
FAU - Hsueh, Chung-Tsen
AU  - Hsueh CT
LA  - eng
PT  - Journal Article
DEP - 20120430
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 2.1.3.3 (Ornithine Carbamoyltransferase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - *Apoptosis
MH  - Arginase/*metabolism
MH  - Arginine/*deficiency
MH  - Blotting, Western
MH  - Cell Survival
MH  - Humans
MH  - Male
MH  - Ornithine Carbamoyltransferase/metabolism
MH  - Prostatic Neoplasms/*metabolism/*pathology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Recombinant Proteins/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC3403903
EDAT- 2012/05/02 06:00
MHDA- 2012/12/21 06:00
PMCR- 2012/04/30
CRDT- 2012/05/02 06:00
PHST- 2012/03/28 00:00 [received]
PHST- 2012/04/30 00:00 [accepted]
PHST- 2012/05/02 06:00 [entrez]
PHST- 2012/05/02 06:00 [pubmed]
PHST- 2012/12/21 06:00 [medline]
PHST- 2012/04/30 00:00 [pmc-release]
AID - 1756-8722-5-17 [pii]
AID - 10.1186/1756-8722-5-17 [doi]
PST - epublish
SO  - J Hematol Oncol. 2012 Apr 30;5:17. doi: 10.1186/1756-8722-5-17.