Induction of cell growth arrest and apoptotic cell death in human breast cancer MCF-7 cells by the COX-1 inhibitor FR122047.
Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzyme cyclooxygenase (COX), are known to have a potent anti-tumorigenic activity in various cancers. However, the responsible molecular mechanisms of COX inhibition in breast cancer cells remain to be completely elucidated. We examined the effect of the selective COX-1 inhibitor, FR122047 and the selective COX-2 inhibitor, SC791 on cell growth and apoptosis in human breast cancer MCF-7 cells which exhibited a high basal level of COX-1 expression. Compared to SC791, FR122047 treatment led to a distinct suppression of cell growth in MCF-7 cells. Upon FR122047 treatment, there were apparent increases in the ratio of Bax to Bcl-2, mitochondrial cytochrome c release, and apoptosis in MCF-7 cells. Our data showed that treatment of caspase-8 inhibitor could significantly suppress the cleavage of the effector caspase-7 and PARP in FR122047-treated MCF-7 cells which are caspase-3-deficient breast cancer cells, indicating that the induction of apoptosis by FR122047 is significantly dependent on caspase-8 activity in MCF-7 breast cancer cells. Our data suggest that the NSAID FR122047 may have an anti-cancer potential in breast cancer.
Jeong
Hyo-Soon
HS
Department of Animal Biotechnology, Animal Resources Research Center, and RCTCP, Konkuk University, Gwangjin-ku, Seoul 143-701, South Korea.
Kim
Jung-Hyun
JH
Choi
Hye Yeon
HY
Lee
Eung-Ryoung
ER
Cho
Ssang-Goo
SG
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002278:Carcinoma in Situ / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D010879:Piperazines; C553330:SC 791; D013449:Sulfonamides; D013844:Thiazoles; C085131:1-((4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl)-4-methylpiperazine; D051545:Cyclooxygenase 1