Arginine deprivation, autophagy, apoptosis (aaa) for the treatment of melanoma

Niramol Savaraj, M. You, C. Wu, Medhi Wangpaichitr, M. T. Kuo, Lynn G Feun

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The majority of melanoma cells do not express argininosuccinate synthetase (ASS), and hence cannot synthesize arginine from citrulline. Their growth and proliferation depend on exogenous supply of arginine. Arginine degradation using arginine deiminase (ADI) leads to growth inhibition and eventually cell death while normal cells which express ASS can survive. This notion has been translated into clinical trial. Pegylated ADI (ADI-PEG20) has shown antitumor activity in melanoma. However, the sensitivity to ADI is different among ASS(-) melanoma cells. We have investigated and reviewed the signaling pathways which are affected by arginine deprivation and their consequences which lead to cell death. We have found that arginine deprivation inhibits mTOR signaling but leads to activation of MEK and ERK with no changes in BRAF. These changes most likely lead to autophagy, a possible mechanism to survive by recycling intracellular arginine. However apoptosis does occur which can be both caspase-dependent or independent. In order to increase the therapeutic efficacy of this form of treatment, one should consider adding other agent(s) which can drive the cells toward apoptosis or inhibit the autophagic process.

Original languageEnglish
Pages (from-to)405-412
Number of pages8
JournalCurrent Molecular Medicine
Volume10
Issue number4
DOIs
StatePublished - Jun 18 2010

Fingerprint

Autophagy
Arginine
Melanoma
Argininosuccinate Synthase
Apoptosis
Cell death
Cell Death
Citrulline
Mitogen-Activated Protein Kinase Kinases
Recycling
Growth
Caspases
Chemical activation
Clinical Trials
Degradation
arginine deiminase

Keywords

  • Arginine deiminase
  • Argininosuccinate synthetase
  • Melanoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

Cite this

Arginine deprivation, autophagy, apoptosis (aaa) for the treatment of melanoma. / Savaraj, Niramol; You, M.; Wu, C.; Wangpaichitr, Medhi; Kuo, M. T.; Feun, Lynn G.

In: Current Molecular Medicine, Vol. 10, No. 4, 18.06.2010, p. 405-412.

Research output: Contribution to journalArticle

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