Chemotherapeutic properties of phospho-nonsteroidal anti-inflammatory drugs, a new class of anticancer compounds.
Chemotherapeutic properties of phospho-nonsteroidal anti-inflammatory drugs, a new class of anticancer compounds.
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DOI：
10.1158/0008-5472.can-11-2349
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Rigas B
中科院分区：
文献类型：
--
作者：
Huang L;Mackenzie GG;Sun Y;Ouyang N;Xie G;Vrankova K;Komninou D;Rigas B
Non-steroidal anti-Inflammatory drugs (NSAIDs) exhibit antineoplastic properties, but conventional NSAIDs do not fully meet safety and efficacy criteria for use as anti-cancer agents. In this study, we evaluated the chemotherapeutic efficacy of five novel phospho-NSAIDs, each of which includes in addition to the NSAID moiety a diethylphosphate linked through a butane moiety. All five compounds inhibited the growth of human breast, colon and pancreatic cancer cell lines with micromolar potency. In vivo investigations confirmed the antitumor activity of phospho-aspirin (PA) and phospho-sulindac (PS) in inhibiting tumor growth in established human xenograft models, where cell proliferation was suppressed and apoptosis enhanced in the absence of detectable animal toxicity. Notably, all of the phospho-NSAIDs tested induced reactive oxygen and nitrogen species in cultured cells, with PA and PS inducing detectable levels of oxidative stress in vivo that were associated positively with apoptosis and negatively with proliferation. Potentially explaining these effects, all of the phospho-NSAIDs tested also inhibited the thioredoxin system and the redox sensitive transcription factor NF-κB. Taken together, our findings demonstrate the strong anticancer efficacy and promising safety of phospho-NSAIDs in preclinical models of breast, colon and pancreatic cancer, suggesting further evaluation as anticancer agents..
