Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy.
Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy.
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DOI：
10.1158/1940-6207.capr-15-0119
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Shannon J
中科院分区：
文献类型：
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作者：
Atwell LL;Zhang Z;Mori M;Farris P;Vetto JT;Naik AM;Oh KY;Thuillier P;Ho E;Shannon J
流行病学研究表明，十字花科蔬菜对乳腺癌有保护作用。萝卜硫素(SFN)是一种从十字花科植物中提取的活性食物成分，已被证明在乳腺癌化学预防中是有效的。本研究评价了三七总皂苷对血液和乳腺组织中选择性生物标志物的化学预防作用。在一项为期2-8周的双盲随机对照试验中，54名乳房X光检查异常并计划接受乳房活检的妇女被随机分成两组，分别服用安慰剂或提供SFN的葡萄糖胺(GFN)补充剂(n=27)。检测良性乳腺、导管原位癌(DCIS)和浸润性导管癌(IDC)乳腺组织介入治疗前后血、尿SFN代谢产物、外周血单个核细胞(PBMC)组蛋白脱乙酰酶(HDAC)活性和组织标志物(H3K18ac、H3K9ac、HDAC3、HDAC6、Ki-67、p21)的变化。在补充组中，良性组织中Ki-67(p=0.003)和hDAC3(p=0.044)水平显著降低。经过多重比较调整后，干预前后这些生物标志物的变化在不同治疗组之间没有显著差异。补充GFN与PBMC HDAC活性显著降低有关(p=0.04)。在比较治疗组时，未观察到SFN与所检查的组织生物标记物之间的显著关联。这项研究提供的证据表明，补充GFN几周是安全的，但可能不足以产生乳腺组织肿瘤生物标记物的变化。未来采用更大样本量的研究应该评估替代剂量和持续时间方案，以告知饮食SFN在乳腺癌化学预防中的策略。
Epidemiological studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2-8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ (DCIS), or invasive ductal carcinoma (IDC) breast tissues. Within the supplement group, Ki-67 (p = 0.003) and HDAC3 (p = 0.044) levels significantly decreased in benign tissue. Pre-to-post-intervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (p = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention.