Arginine deprivation as a new treatment strategy for head and neck cancer

Cheng Chih Huang, Sen Tien Tsai, Ching Chuan Kuo, Jeffrey S. Chang, Ying Tai Jin, Jang Yang Chang, Jenn Ren Hsiao

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Objectives: Arginine is a nonessential amino acid which can regulate tumor growth. Argininosuccinate synthetase (ASS) is the rate-limiting enzyme for de novo arginine production. The expression pattern of ASS and the feasibility of arginine deprivation therapy in head and neck cancer have not been investigated. Materials and methods: The growth-inhibitory effect of arginine deprivation therapy was assessed either by proliferation assay with head and neck cancer cells cultured in arginine-free medium, or by tetrazolium/formazan dye assay with cells treated with an arginine-depleting drug (arginine deiminase, ADI). The tumor ASS status of 73 oral squamous carcinoma (OSCC) patients was then evaluated immunohistochemically and subsequently correlated with the corresponding clinicopathological parameters. Results: Head and neck cancer cells cultured in arginine-free medium either completely stopped proliferating, or proliferated minimally. In addition, ADI treatment inhibited the growth of all 8 head and neck cancer cell lines to different degrees. Although cellular ASS level did not correlate well with ADI-sensitivity among these cell lines, knockdown of endogenous ASS potentiated the growth-inhibitory effect of ADI in each individual cell line (FaDu and OEC-M1). In multivariable analysis, high tumor ASS level independently predicted an unfavorable disease-free survival in OSCC patients. Conclusion: High tumor ASS status is an independent variable predicting a poor disease-free survival in OSCC patients. Arginine deprivation therapy may potentially be used as a new approach to treat head and neck cancer.

Original languageEnglish
Pages (from-to)1227-1235
Number of pages9
JournalOral Oncology
Issue number12
Publication statusPublished - Dec 2012
Externally publishedYes


  • Arginine
  • Argininosuccinate synthetase (ASS)
  • Head and neck cancer
  • Immunohistochemistry (IHC)
  • Oral squamous cell carcinoma (OSCC)

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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