Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer.
Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer.
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姜黄衍生的姜黄素和乳腺癌相关代谢产物的生物活性。
DOI：
10.2174/1381612811319340013
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发表时间：
2013
影响因子：
3.1
通讯作者：
Funk JL
中科院分区：
文献类型：
--
作者：
Wright LE;Frye JB;Gorti B;Timmermann BN;Funk JL
姜黄素是从姜黄中提取的三种主要姜黄素之一，其化疗作用已被报道，但与传统药物制剂类似的姜黄素复合提取物的作用，以及这三种姜黄素及其代谢物作为抗癌剂的相对重要性，在很大程度上尚未被探索。这些研究记录了化学复合物姜黄提取物相对于姜黄素对人乳腺癌细胞生长和肿瘤细胞分泌甲状旁腺激素相关蛋白（PTHrP）的药效学影响，PTHrP是癌症骨转移的重要驱动因素。最后，在相同的终点上评估姜黄素结构相关代谢物的相对影响。我们报道了3种含有姜黄素的姜黄提取物，在包含额外的天然化学物质（精油和/或极性化合物）方面有所不同，当浓度标准化到姜黄素含量时，它们在抑制人乳腺癌MDA-MB-231细胞生长（IC50= 10-16μg /mL）和溶骨性PTHrP的分泌（IC50= 2-3μg /mL）方面是相同的。此外，这些作用是姜黄素特异性的，因为与植物相关的含有姜辣素的提取物没有作用。姜黄素和双去甲氧基姜黄素对天然的姜黄素混合物（IC50=58 μM）均有相当的抑制作用，而去甲氧基姜黄素对细胞生长无影响。然而，每种姜黄素对PTHrP分泌的抑制程度（IC50= 22-31μM）与姜黄素混合物（IC50=16 μM）相同。降解性姜黄素代谢物（香兰素和阿魏酸）对细胞生长和PTHrP没有抑制作用，而还原性代谢物（四氢姜黄素）对细胞生长和PTHrP分泌有抑制作用，但浓度≥10倍高于姜黄素。这些研究强调了姜黄素在姜黄抗乳腺癌作用中的结构和生物学重要性，并反驳了最近研究的某些姜黄素代谢物介导这些抗癌作用的说法。
While the chemotherapeutic effect of curcumin, one of three major curcuminoids derived from turmeric, has been reported, largely unexplored are the effects of complex turmeric extracts more analogous to traditional medicinal preparations, as well as the relative importance of the three curcuminoids and their metabolites as anti-cancer agents. These studies document the pharmacodynamic effects of chemically-complex turmeric extracts relative to curcuminoids on human breast cancer cell growth and tumor cell secretion of parathyroid hormone-related protein (PTHrP), an important driver of cancer bone metastasis. Finally, relative effects of structurally-related metabolites of curcuminoids were assessed on the same endpoints. We report that 3 curcuminoid-containing turmeric extracts differing with respect to the inclusion of additional naturally occurring chemicals (essential oils and/or polar compounds) were equipotent in inhibiting human breast cancer MDA-MB-231 cell growth (IC50=10–16μg/mL) and secretion of osteolytic PTHrP (IC50=2–3μg/mL) when concentrations were normalized to curcuminoid content. Moreover, these effects were curcuminoid-specific, as botanically-related gingerol containing extracts had no effect. While curcumin and bis-demethoxycurcumin were equipotent to each other and to the naturally occurring curcuminoid mixture (IC50=58 μM), demethoxycurcumin was without effect on cell growth. However, each of the individual curcuminoids inhibited PTHrP secretion (IC50=22–31μM) to the same degree as the curcuminoid mixture (IC50=16 μM). Degradative curcuminoid metabolites (vanillin and ferulic acid) did not inhibit cell growth or PTHrP, while reduced metabolites (tetrahydrocurcuminoids) had inhibitory effects on cell growth and PTHrP secretion but only at concentrations ≥10-fold higher than the curcuminoids. These studies emphasize the structural and biological importance of curcuminoids in the anti-breast cancer effects of turmeric and contradict recent assertions that certain of the curcuminoid metabolites studied here mediate these anti-cancer effects.
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影响因子：
6.1
作者：
Funk JL;Frye JB;Oyarzo JN;Zhang H;Timmermann BN
通讯作者：
Timmermann BN
影响因子：
5.1
作者：
Funk, Janet L.;Frye, Jennifer B.;Timmermann, Barbara N.
通讯作者：
Timmermann, Barbara N.
影响因子：
2.8
作者：
Ji, Jun-Ling;Huang, Xian-Feng;Zhu, Hai-Liang
通讯作者：
Zhu, Hai-Liang
影响因子：
11.9
作者：
Gupta SC;Prasad S;Kim JH;Patchva S;Webb LJ;Priyadarsini IK;Aggarwal BB
通讯作者：
Aggarwal BB
影响因子：
5.2
作者：
Dempe, Julia S.;Pfeiffer, Erika;Metzler, Manfred
通讯作者：
Metzler, Manfred