A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models.
A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models.
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DOI：
10.1016/j.neo.2018.06.003
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Wu D
中科院分区：
文献类型：
--
作者：
Mamouni K;Zhang S;Li X;Chen Y;Yang Y;Kim J;Bartlett MG;Coleman IM;Nelson PS;Kucuk O;Wu D
前列腺癌（PCa）的高患病率和长潜伏期为通过饮食和营养方法控制疾病进展提供了独特的机会。我们开发了ProFine，一种标准化的木犀草素，槲皮素和山奈酚的组合物，并研究了其作为临床前模型中PCa营养药物的潜力。ProFine的三种成分显示出协同的体外细胞毒性，并有效地诱导PCa细胞凋亡。ProFine显著影响PCa细胞的转录组，抑制雄激素受体的表达，并抑制雄激素调节基因。ProFine口服给药在小鼠中未表现出明显的毒性，并且三种成分保留了各自的药代动力学和生物利用度特征。重要的是，ProFine显著延缓了无胸腺裸鼠中PCa异种移植物的生长，并延长了动物的存活期。这项研究提供了临床前证据，支持ProFine作为一种安全、有效和经济实惠的干预措施来控制PCa进展并改善临床结局。
The high prevalence and long latency period of prostate cancer (PCa) provide a unique opportunity to control disease progression with dietary and nutraceutical approaches. We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, and investigated its potential as a nutraceutical for PCa in preclinical models. The three ingredients of ProFine demonstrated synergistic in vitro cytotoxicity and effectively induced apoptosis in PCa cells. ProFine markedly affected the transcriptome of PCa cells, suppressed the expression of androgen receptor, and inhibited androgen-regulated genes. Oral administration of ProFine did not exhibit obvious toxicities in mice, and the three ingredients retained their individual pharmacokinetic and bioavailability profiles. Importantly, ProFine significantly retarded the growth of PCa xenografts in athymic nude mice and extended the survival of animals. This study provides preclinical evidence supporting the promise of ProFine as a safe, efficacious, and affordable intervention to control PCa progression and improve clinical outcomes.
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影响因子：
5.6
作者：
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