Cytotoxic effects of celecoxib on Raji lymphoma cells correlate with aggravated endoplasmic reticulum stress but not with inhibition of cyclooxygenase-2.
Inhibition of cyclooxygenase 2 (COX-2) by the selective COX-2 inhibitor celecoxib has been suggested as potentially useful for B-cell lymphoma therapy. However, additional pharmacological activities of celecoxib have been discovered and have challenged the notion that its antitumor effects are mediated primarily via the inhibition of COX-2. To shed light on this issue, we have investigated the effects of different pharmacological agents with greatly varying COX-2 inhibitory potency in Raji lymphoma cells in vitro. We found that cytotoxic potency of these compounds did not at all correlate with their COX-2 inhibitory activity; in fact, the most potent COX-2 inhibitors lacked the ability to kill Raji cells. Instead, the cytotoxic outcome was closely aligned with these agents' ability to trigger endoplasmic reticulum (ER) stress, which could be further enhanced by bortezomib, an agent with known ER stress-inducing potency. Together, these results indicate that celecoxib's cytotoxic effects on Raji lymphoma cells do not involve the inhibition of COX-2.
Chen
Szu-Ting
ST
Biochemistry & Molecular Biology, University of Southern California, Los Angeles, CA 90089-9094, USA.
Thomas
Simmy
S
Gaffney
Kevin J
KJ
Louie
Stan G
SG
Petasis
Nicos A
NA
Schönthal
Axel H
AH
D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D000068579:Celecoxib; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004721:Endoplasmic Reticulum / Q000473:pathology*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013312:Stress, Physiological / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
D001897:Boronic Acids; D052246:Cyclooxygenase 2 Inhibitors; D011719:Pyrazines; D011720:Pyrazoles; D013449:Sulfonamides; D000069286:Bortezomib; D051546:Cyclooxygenase 2; D000068579:Celecoxib