Jian Ye1, Meredith Montero, Brendan C Stack. 1. Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Ark., USA.
Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) can become resistant to some chemotherapy and becomes a clinical challenge when it recurs. There are few agents identified for second-line treatment of resistant head and neck cancer. Therefore, we evaluated the role of fusaric acid (FA) as a possible agent for treatment for chemotherapy-resistant laryngeal squamous cell carcinoma. METHODS: The HEp2 and docetaxel-resistant HEp2 (HEp-Doc) cell lines were created from human laryngeal cancer. Cell lines were exposed to FA at increasing concentrations (0.1, 0.3, and 0.5 mM) and time intervals of 24, 48, 72, and 96 h. The effects on cell survival, apoptosis, and cytokine and protein expression were analyzed. RESULTS: FA treatment in the HEp-Doc cells showed greater reduction of cell number and colony-forming units and more apoptosis when compared to HEp2 and required less time to reduce cell number. Four cytokines were detected in HEp2 cancer cells that increased with FA treatment. Pro-caspase-9 and -7 and poly (ADP-ribose) polymerase also increased with FA treatment. CONCLUSION: FA may be an agent to be considered in cases of HNSCC treatment resistance or post-docetaxel recurrence. Further investigation of FA in vitro and in vivo is indicated.
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) can become resistant to some chemotherapy and becomes a clinical challenge when it recurs. There are few agents identified for second-line treatment of resistant head and neck cancer. Therefore, we evaluated the role of fusaric acid (FA) as a possible agent for treatment for chemotherapy-resistant laryngeal squamous cell carcinoma. METHODS: The HEp2 and docetaxel-resistant HEp2 (HEp-Doc) cell lines were created from humanlaryngeal cancer. Cell lines were exposed to FA at increasing concentrations (0.1, 0.3, and 0.5 mM) and time intervals of 24, 48, 72, and 96 h. The effects on cell survival, apoptosis, and cytokine and protein expression were analyzed. RESULTS: FA treatment in the HEp-Doc cells showed greater reduction of cell number and colony-forming units and more apoptosis when compared to HEp2 and required less time to reduce cell number. Four cytokines were detected in HEp2 cancer cells that increased with FA treatment. Pro-caspase-9 and -7 and poly (ADP-ribose) polymerase also increased with FA treatment. CONCLUSION: FA may be an agent to be considered in cases of HNSCC treatment resistance or post-docetaxel recurrence. Further investigation of FA in vitro and in vivo is indicated.