Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on Burkitt's lymphoma in vitro and in vivo.
The nonsteroidal anti-inflammatory drug (NSAID) celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has shown some promising results as an anti-cancer drug. However, the question arose as to whether or not its COX-2-inhibitory function is required for its anti-tumorigenic properties. We therefore employed dimethyl-celecoxib (DMC), which is a close structural analog of celecoxib that lacks COX-2-inhibitory function, to investigate this question. By performing a combination of in vitro and in vivo studies with Burkitt's lymphoma cells, we found that DMC potently mimics all of the anti-proliferative and anti-tumorigenic effects of celecoxib. In cell culture, DMC effectively inhibits cell proliferation through the down-regulation of cyclins A and B and the ensuing loss of cyclin-dependent kinase activity. This effect appears to take place in vivo as well and results in significantly (p<.002) reduced tumor growth in experimental animals. Thus, our results demonstrate that the anti-proliferative and anti-tumorigenic properties of celecoxib and DMC are indistinguishable, at least in Burkitt's lymphoma cells, and therefore, that the COX-2-inhibitory function is not required for these effects.
Kardosh
Adel
A
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089-9094, USA.
Wang
Weijun
W
Uddin
Jasim
J
Petasis
Nicos A
NA
Hofman
Florence M
FM
Chen
Thomas C
TC
Schönthal
Axel H
AH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
C506698:2,5-dimethylcelecoxib; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone