Combinatorial bioactive botanicals re-sensitize tamoxifen treatment in ER-negative breast cancer via epigenetic reactivation of ERα expression.
Combinatorial bioactive botanicals re-sensitize tamoxifen treatment in ER-negative breast cancer via epigenetic reactivation of ERα expression.
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联合生物活性植物体通过ERα表达的表观遗传重新激活ER阴性乳腺癌中的他莫昔芬治疗。
DOI：
10.1038/s41598-017-09764-3
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发表时间：
2017-08-24
影响因子：
4.6
通讯作者：
Tollefsbol TO
中科院分区：
文献类型：
--
作者：
Li Y;Meeran SM;Tollefsbol TO
传统的癌症预防主要集中在可能不够有效的单一化学预防化合物上。我们试图研究表观遗传生物活性植物药（包括绿色茶多酚（GTP）中的表没食子儿茶素-3-没食子酸酯（EGCG）和西兰花芽（BSp）中的萝卜硫素（SFN））对中和雌激素受体-α（ERα）中的表观遗传畸变的潜在组合效应，从而增强ERα阴性乳腺癌的抗激素治疗效果。我们的研究结果表明，这种联合治疗重新敏感ERα依赖性细胞抑制反应的雌激素拮抗剂，他莫昔芬（TAM），至少部分通过表观遗传再激活ERα表达在ERα阴性乳腺癌细胞。进一步的体内研究显示，GTP和BSp的组合饮食显著抑制ERα阴性小鼠异种移植物中的乳腺肿瘤生长，尤其是当与TAM治疗组合时。这种新的治疗方案可以通过组蛋白修饰和ERα启动子中转录因子复合物的募集变化导致染色质结构的重塑，从而有助于ERα再激活和抗激素治疗的再致敏化疗疗效。我们的研究表明，来自GTP和BSp的组合生物活性植物药在抑制ERα阴性乳腺癌方面非常有效，至少部分是由于ERα的表观遗传再活化，这反过来又增加了体外和体内TAM依赖性抗雌激素化疗敏感性。
Conventional cancer prevention has primarily focused on single chemopreventive compounds that may not be sufficiently efficacious. We sought to investigate potential combinatorial effects of epigenetic bioactive botanicals including epigallocatechin-3-gallate (EGCG) in green tea polyphenols (GTPs) and sulforaphane (SFN) in broccoli sprouts (BSp) on neutralizing epigenetic aberrations in estrogen receptor-α (ERα) leading to enhanced anti-hormone therapeutic efficacy in ERα-negative breast cancer. Our results showed that this combinatorial treatment re-sensitized ERα-dependent cellular inhibitory responses to an estrogen antagonist, tamoxifen (TAM), via at least in part, epigenetic reactivation of ERα expression in ERα-negative breast cancer cells. Further in vivo studies revealed the combinatorial diets of GTPs and BSp significantly inhibited breast tumor growth in ERα-negative mouse xenografts, especially when combined with TAM treatment. This novel treatment regimen can lead to remodeling of the chromatin structure by histone modifications and recruitment changes of transcriptional factor complex in the ERα promoter thereby contributing to ERα reactivation and re-sensitized chemotherapeutic efficacy of anti-hormone therapy. Our studies indicate that combinatorial bioactive botanicals from GTPs and BSp are highly effective in inhibiting ERα-negative breast cancer due at least in part to epigenetic reactivation of ERα, which in turn increases TAM-dependent anti-estrogen chemosensitivity in vitro and in vivo.
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影响因子：
7.4
作者：
Gross, Jennifer M;Yee, Douglas
通讯作者：
Yee, Douglas
营养植物体抑制早期乳腺癌的结合表观遗传机制和功效。
影响因子：
3.8
作者：
Li Y;Buckhaults P;Cui X;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
4.2
作者：
Fang, Mingzhu;Chen, Dapeng;Yang, Chung S.
通讯作者：
Yang, Chung S.
影响因子：
4.2
作者：
Ho, Emily;Clarke, John D.;Dashwood, Roderick H.
通讯作者：
Dashwood, Roderick H.
影响因子：
37.3
作者：
Li Y;Meeran SM;Patel SN;Chen H;Hardy TM;Tollefsbol TO
通讯作者：
Tollefsbol TO