A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties
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- 作者：Irida Kastrati ; Vladislav A. Litosh ; Shuangping Zhao ; Manuel Alvarez…
- 关键词：Breast cancer ; Aspirin ; Cancer stem cells ; Fumarate ; NFκB
- 刊名：BMC Cancer
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：15
- 期：1
- 全文大小：1,845 KB
- 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
- 出版者：BioMed Central
- ISSN：1471-2407
文摘
Introduction Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored.