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Tolfenamic acid induces apoptosis and growth inhibition in head and neck cancer: involvement of NAG-1 expressio

Kang, SU; Shin, YS; Hwang, HS; Baek, SJ; Lee, SH; Kim, CH
PloS one, 7(4):e34988-e34988, 2012
Journal Title
PloS one
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.
MeSH terms
AnimalsAntineoplastic Agents/*pharmacology/therapeutic useApoptosis/*drug effectsCarcinoma, Squamous Cell/*drug therapyCell Line, TumorCell Proliferation/drug effectsGene ExpressionGrowth Differentiation Factor 15/genetics/*metabolismHead and Neck Neoplasms/*drug therapyHumansMembrane Potential, Mitochondrial/drug effectsMiceMice, Inbred BALB CMice, NudeTranscriptional Activation/drug effectsXenograft Model Antitumor Assaysortho-Aminobenzoates/*pharmacology/therapeutic use
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
AJOU Authors
신, 유섭김, 철호
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