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Cytotoxic effects of celecoxib on Raji lymphoma cells correlate with aggravated endoplasmic reticulum stress but not with inhibition of cyclooxygenase-2.

Abstract：

: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.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Chen ST,Thomas S,Gaffney KJ,Louie SG,Petasis NA,Schönthal AH

doi

10.1016/j.leukres.2009.09.028

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

250-3

issue

2

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(09)00488-3

journal_volume

34

pub_type

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