Combination of Arginine deprivation with TRAIL treatment as a targeted-therapy for mesothelioma

Medhi Wangpaichitr, Chunjing Wu, Gregory Bigford, George Theodoropoulos, Min You, Ying Ying Li, Javier Verona-Santos, Lynn G. Feun, Dao M. Nguyen, Niramol Savaraj

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

In the present study we present data to show that certain tumor cells including malignant pleural mesothelioma (MPM) cells do not express argininosuccinate synthetase (ASS), and thus are unable to synthesize arginine from citrulline. Exposure of these ASS-negative cells to the arginine degrading enzyme, arginine deiminase (ADIPEG20), for 72 h results in significant increases in cleaved caspase-3. Importantly, this apoptotic signal is further strengthened by the addition of TNF-related apoptosisinducing ligand (TRAIL). Using flow cytometry, we showed that the combination treatment (ADI-PEG20 at 50 ng/ml and TRAIL at 10 ng/ml) for 24 h resulted in profound cell death with 67% of cells positive for caspase-3 activity, while ADIPEG20 alone or TRAIL alone resulted in only 10-15% cell death. This positive amplification loop is mediated through the cleavage of proapototic protein "BID". Conclusion: Our work represents a new strategy for treating patients with malignant pleural mesothelioma using targeted molecular therapeutics based on selected tumor markers, thus avoiding the use of potentially cytotoxic chemotherapy.

Original languageEnglish (US)
Pages (from-to)6991-6999
Number of pages9
JournalAnticancer research
Volume34
Issue number12
StatePublished - Dec 1 2014

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Keywords

  • Arginine deprivation
  • Mesothelioma
  • TNF-related apoptosis-inducing ligand (TRAIL).

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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