title: Tolfenamic acid induces apoptosis and growth inhibition in head and neck cancer: involvement of NAG-1 expression.
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.
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015533:Transcriptional Activation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D062367:ortho-Aminobenzoates / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid