Related Experiment Video
Updated: May 19, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Arginine deprivation as a new treatment strategy for head and neck cancer
Cheng-Chih Huang1, Sen-Tien Tsai, Ching-Chuan Kuo
1Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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.
Insights
Argininosuccinate synthetase (ASS) high expression predicts poor survival in head and neck cancer. Arginine deprivation therapy shows promise for treating these cancers.
Area of Science:
- Oncology
- Cancer Biology
- Biochemistry
Background:
- Arginine is a nonessential amino acid crucial for tumor growth.
- Argininosuccinate synthetase (ASS) is the key enzyme in arginine synthesis.
- The role of ASS and arginine deprivation therapy in head and neck cancer remains unexplored.
Purpose of the Study:
- To investigate the expression of ASS in head and neck cancers.
- To evaluate the efficacy of arginine deprivation therapy in head and neck cancer models.
- To determine the prognostic value of ASS in oral squamous cell carcinoma (OSCC).
Main Methods:
- Assessed growth inhibition of head and neck cancer cells using arginine-free medium and arginine deiminase (ADI).
- Immunohistochemically analyzed tumor ASS status in 73 OSCC patients.
- Correlated ASS status with clinicopathological parameters and patient survival.
Main Results:
- Arginine deprivation significantly inhibited head and neck cancer cell proliferation.
- ADI treatment demonstrated varying degrees of growth inhibition across cell lines.
- High tumor ASS levels independently predicted unfavorable disease-free survival in OSCC patients.
- Knockdown of ASS enhanced ADI's growth-inhibitory effect.
Conclusions:
- Elevated tumor ASS expression is a significant independent predictor of poor disease-free survival in OSCC.
- Arginine deprivation therapy presents a potential novel therapeutic strategy for head and neck cancers.
Related Concept Videos
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Treatment Resistant Cancers
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Targeted Cancer Therapies
There are several types of targeted therapies against specific...