Effects of fusaric acid treatment on HEp2 and docetaxel-resistant HEp2 laryngeal squamous cell carcinoma.
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.


CONCLUSIONS
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.
Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Ark., USA.
Jian
J
Ye
Meredith
M
Montero
Brendan C
BC
Stack
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005669:Fusaric Acid / Q000633:toxicity*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D043823:Taxoids / Q000633:toxicity; D013997:Time Factors
D000970:Antineoplastic Agents; D016207:Cytokines; D043823:Taxoids; D000077143:Docetaxel; D011065:Poly(ADP-ribose) Polymerases; D053179:Caspase 7; D053453:Caspase 9; D005669:Fusaric Acid