Fusaric acid: a novel agent and mechanism to treat HNSCC
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Published on: January 18, 2017
Brendan C Stack1, J Paul Hansen, James M Ruda
1Division of Otolaryngology-HNS, Pennsylvania State University College of Medicine, Hershey, PA 17003, USA. bstack@psu.edu
Objective:
A new class of carboxylic acids has tumoricidal activity for head and neck squamous cell cancer (HNSCC). Fusaric acid (FA) can chelate divalent cations, especially zinc, and inactivate zinc finger proteins involved in DNA repair and protein synthesis.
Methods:
2 squamous carcinoma lines were utilized for in vitro and in vivo portions of this study. Cell counting and flow cytometry were used to analyze cells in culture in treatment and control groups over 96 hours. HNSCC subcutaneous implants were created in treatment and control groups of BALB-c nude mice (N = 30).
Results:
In vitro studies demonstrated significant changes in cell numbers and cell cycle. In vivo studies of daily intralesional therapy for 1 month also showed reduced onset of growth and overall growth compared to controls.
Conclusion:
FA appears to have a tumoristatic/tumoricidal effect on HNSCC. Further nude mice studies are needed to optimize dosing and administration regimens for FA in anticipation of clinical trials.
Insights
Fusaric acid (FA) shows tumoricidal effects against head and neck squamous cell cancer (HNSCC). This new carboxylic acid therapy warrants further investigation for potential clinical applications in HNSCC treatment.
Area of Science:
- Oncology
- Cancer Biology
- Medicinal Chemistry
Background:
- Head and neck squamous cell cancer (HNSCC) remains a significant health challenge.
- A novel class of carboxylic acids exhibits promising tumoricidal activity.
- Fusaric acid (FA) is identified as a potential therapeutic agent due to its ability to chelate zinc and disrupt critical cellular processes.
Purpose of the Study:
- To evaluate the tumoricidal activity of Fusaric acid (FA) against head and neck squamous cell cancer (HNSCC).
- To investigate the in vitro and in vivo effects of FA on HNSCC cell lines and tumor models.
Main Methods:
- Utilized two squamous carcinoma cell lines for in vitro and in vivo experiments.
- Employed cell counting and flow cytometry to analyze cellular changes over 96 hours.
- Established HNSCC subcutaneous implants in BALB-c nude mice for in vivo efficacy assessment.
Main Results:
- In vitro studies revealed significant alterations in HNSCC cell numbers and cell cycle progression.
- In vivo studies demonstrated that daily intralesional FA therapy reduced tumor growth onset and overall tumor burden in mice.
- FA exhibited a notable tumoristatic and potentially tumoricidal effect on HNSCC models.
Conclusions:
- Fusaric acid (FA) demonstrates significant potential as an anti-cancer agent for HNSCC.
- Further preclinical studies in nude mice are essential to optimize FA dosage and administration.
- These findings pave the way for future clinical trials investigating FA for HNSCC treatment.
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