Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene.
We have investigated whether NAG-1 is induced in oral cavity cancer cells by various NSAIDs and if apoptosis induced by NSAIDs can be linked directly with the induction of NAG-1. NAG-1 expression was increased by diclofenac, aceclofenac, indomethacin, ibuprofen, and sulindac sulfide, in the order of NAG-1 induction, but not by acetaminophen, piroxicam or NS-398. Diclofenac was the most effective NAG-1 inducer. Incubation with diclofenac inhibited cell proliferation and induced apoptosis. The expression of NAG-1 was observed in advance of the induction of apoptosis. Conditioned medium from NAG-1-overexpressing Drosophila cells inhibited SCC 1483 cells proliferation and induced apoptosis. In summary, some NSAIDs induce NAG-1 expression in oral cavity cancer cells and the induced NAG-1 protein appears to mediate apoptosis. Therefore, NSAIDs may be considered as a possible chemopreventive agent against oral cavity cancer.
Kim
Kyung-Su
KS
Department of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, Republic of Korea. ydrhinol@yumc.yonsei.ac.kr
Yoon
Joo-Heon
JH
Kim
Jin Kook
JK
Baek
Seung Joon
SJ
Eling
Thomas E
TE
Lee
Won Jae
WJ
Ryu
Ji-Hwan
JH
Lee
Jeung Gweon
JG
Lee
Joo-Hwan
JH
Yoo
Jong-Bum
JB
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055436:Growth Differentiation Factor 15; D006801:Humans; D009055:Mouth / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D011994:Recombinant Proteins