Abstract
Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is induced by nonsteroidal anti-inflammatory drugs and possesses proapoptotic and antitumorigenic activities. Although tolfenamic acid (TA) induces apoptosis in head and neck cancer cells, the relationship between NAG-1 and TA has not been determined. This study investigated the induction of apoptosis in head and neck cancer cells treated by TA and the role of NAG-1 expression in this induction. TA reduced head and neck cancer cell viability in a dose-dependent manner and induced apoptosis. The induced apoptosis was coincident with the expression of NAG-1. Overexpression of NAG-1 enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. TA significantly inhibited tumor formation as assessed by xenograft models, and this result accompanied the induction of apoptotic cells and NAG-1 expression in tumor tissue samples. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression in head and neck squamous cell carcinoma, providing an additional mechanistic explanation for the apoptotic activity of TA.
Highlights
With over 500,000 cases worldwide and a high mortality rate, head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in men
We examined the regulation of Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) expression during tolfenamic acid (TA)-induced apoptosis in HNSCC cells
To investigate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the growth of HNSCC cells, the four selected HNSCC cell lines were incubated with varying concentrations (0, 5, 10, 30, 50, 70, 100, 150, and 200 mM) of TA for 16 h and cell viability was measured by the MTT assay
Summary
With over 500,000 cases worldwide and a high mortality rate, head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in men. The overall survival rate has been under 50% for the past 30 years [1]. Some patients achieve long-term survival, those diagnosed with early-stage disease, most patients with this type of cancer have advanced disease at the time of diagnosis. These patients run a risk of recurrent disease, distant metastases, or second primary tumors, and have a median survival of only 6–8 months [2]. The 5-year overall survival rate for patients with advanced HNSCC is around 30%, which is essentially unchanged from the rate recorded two decades ago in spite of various treatment trials. It is of clinical importance to investigate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) as chemopreventive agents
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