Sulforaphane, quercetin and catechins complement each other in elimination of advanced pancreatic cancer by miR-let-7 induction and K-ras inhibition.
Sulforaphane, quercetin and catechins complement each other in elimination of advanced pancreatic cancer by miR-let-7 induction and K-ras inhibition.
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DOI：
10.3892/ijo.2014.2539
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发表时间：
2014-10
影响因子：
5.2
通讯作者：
Herr I
中科院分区：
文献类型：
--
作者：
Appari M;Babu KR;Kaczorowski A;Gross W;Herr I
胰腺导管腺癌（PDA）是所有恶性肿瘤中预后最差的，目前的治疗选择不靶向癌症干细胞（CSC），这可能是极端侵袭性的原因。富含萝卜硫素和槲皮素的膳食剂，例如，在花椰菜中，主要的和最好的研究绿色茶儿茶素EGCG有望作为PDA中的抗CSC剂。我们研究了额外的儿茶素的功效以及这些生物活性剂对干细胞特征和miRNA信号传导的组合。使用了两种已建立的和一种原代PDA细胞系和非恶性胰腺导管细胞。而每一个代理强烈抑制菌落形成，儿茶素ECG和CG比EGCG更有效。绿色茶儿茶素（GTC）的混合物显著抑制细胞活力、迁移、MMP-2和MMP-9的表达、ALDH 1活性、集落和球体形成并诱导细胞凋亡，但GTC与萝卜硫素或槲皮素的组合具有上级优势。在用生物活性剂处理后，miR-let 7-a的表达在癌细胞中被特异性诱导，但在正常细胞中不被诱导，并且其与K-ras抑制相关。这些数据表明，萝卜硫素、槲皮素和GTC在通过诱导miR-let 7-a和抑制K-ras抑制PDA进展方面相互补充。
Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis of all malignancies, and current therapeutic options do not target cancer stem cells (CSCs), which may be the reason for the extreme aggressiveness. The dietary agents sulforaphane and quercetin enriched e.g., in broccoli, and the main and best studied green tea catechin EGCG hold promise as anti-CSC agents in PDA. We examined the efficacy of additional catechins and the combination of these bioactive agents to stem cell features and miRNA signaling. Two established and one primary PDA cell line and non-malignant pancreatic ductal cells were used. Whereas each agent strongly inhibited colony formation, the catechins ECG and CG were more effective than EGCG. A mixture of green tea catechins (GTCs) significantly inhibited viability, migration, expression of MMP-2 and -9, ALDH1 activity, colony and spheroid formation and induced apoptosis, but the combination of GTCs with sulforaphane or quercetin was superior. Following treatment with bioactive agents, the expression of miR-let7-a was specifically induced in cancer cells but not in normal cells and it was associated with K-ras inhibition. These data demonstrate that sulforaphane, quercetin and GTC complement each other in inhibition of PDA progression by induction of miR-let7-a and inhibition of K-ras.
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作者：
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通讯作者：
Herr, Ingrid