期刊
LEUKEMIA RESEARCH
卷 34, 期 2, 页码 250-253出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2009.09.028
关键词
Cyclooxygenase-2; Endoplasmic reticulum stress; CHOP/GADD153
资金
- L.K. Whittier Foundation
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. (C) 2009 Elsevier Ltd. All rights reserved.
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