Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Eur J Pharmacol. 2010 Dec 1;648(1-3):24-30. doi: 10.1016/j.ejphar.2010.08.015. Epub 2010 Sep 6.
Butein is a flavonoid isolated from the bark of Rhus verniciflua Stokes and the flowers of Butea monosperma, and is known to be a potential therapeutic drug for treating inflammation and cancer. Cyclooxygenase (COX) converts arachidonic acid to prostanoids, and increased expression of its isoform COX-2 has been observed in breast cancer tissues. It has been suggested that COX inhibitors can be used as chemopreventive agents against breast carcinogenesis. This study examined the potential suppressive effect of the flavonoid on phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression in the non-tumorigenic MCF-10A and cancerous MCF-7 breast cells. Immunoblot and mRNA analyses revealed that butein at or below 10 μM significantly inhibited PMA-induced COX-2 expression in these breast cells. The blocking of the PKC signaling pathway appeared to be the underlying mechanism. Butein treatment reduced the amount of phospho-mitogen activated protein kinase (MAPK) ERK-1/2, and the total activity of PKC. Activated ERKs might trigger the transcriptional activation of COX-2. Reporter gene assays as well as electrophoretic mobility shift assays (EMSA) illustrated that butein inhibited transcription of this gene. This study showed that butein down-regulated PMA-induced COX-2 expression in both cancerous and non-cancerous breast cells, and such findings could provide the basis for pharmaceutical development of butein.
染料木黄酮是从盐肤木树皮和苏木花中分离得到的一种类黄酮，已知它是一种治疗炎症和癌症的潜在治疗药物。环氧化酶（COX）将花生四烯酸转化为前列腺素，在乳腺癌组织中观察到其同工型 COX-2 的表达增加。已经表明 COX 抑制剂可用作预防乳腺癌发生的化学预防剂。本研究检查了这种黄酮类化合物对佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导的非致瘤 MCF-10A 和致癌 MCF-7 乳腺细胞中 COX-2 表达的潜在抑制作用。免疫印迹和 mRNA 分析表明，在这些乳腺细胞中，染料木黄酮在 10 μM 或以下浓度下可显著抑制 PMA 诱导的 COX-2 表达。阻断蛋白激酶 C（PKC）信号通路似乎是其潜在的机制。染料木黄酮处理减少了磷酸化有丝分裂原激活的蛋白激酶（MAPK）ERK-1/2 的量，以及 PKC 的总活性。激活的 ERKs 可能触发 COX-2 的转录激活。报告基因分析和电泳迁移率变动分析（EMSA）表明，染料木黄酮抑制了该基因的转录。本研究表明，染料木黄酮下调了致癌和非致癌乳腺细胞中 PMA 诱导的 COX-2 表达，这些发现可为染料木黄酮的药物开发提供基础。
