The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines

Min You, Niramol Savaraj, Medhi Wangpaichitr, Chunjing Wu, M. Tien Kuo, Javier Varona-Santos, Dao M. Nguyen, Lynn Feun

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Current treatment for advanced, metastatic melanoma is not very effective, and new modalities are needed. ADI-PEG20 is a drug that specifically targets ASS-negative malignant melanomas while sparing the ASS-expressing normal cells. Although laboratory research and clinical trials showed promising results, there are some ASS-negative cell lines and patients that can develop resistance to this drug. In this report, we combined ADI-PEG20 with another antitumor drug TRAIL to increase the killing of malignant melanoma cells. This combination can greatly inhibit cell growth (to over 80%) and also enhanced cell death (to over 60%) in four melanoma cell lines tested compared with control. We found that ADI-PEG20 could increase the cell surface receptors DR4/5 for TRAIL and that caspase activity correlated with the increased cell death. These two drugs could also increase the level of Noxa while decrease that of survivin. We propose that these two drugs can complement each other by activating the intrinsic and extrinsic apoptosis pathways, thus enhance the killing of melanoma cells.

Original languageEnglish (US)
Pages (from-to)760-766
Number of pages7
JournalBiochemical and biophysical research communications
Volume394
Issue number3
DOIs
StatePublished - Apr 9 2010

Keywords

  • ADI-PEG20
  • Apoptosis
  • Arginine deprivation
  • ASS
  • Melanoma
  • TRAIL

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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