The anti-breast cancer stem cell properties of gold(i)-non-steroidal anti-inflammatory drug complexes.

The anti-breast cancer stem cell properties of gold(i)-non-steroidal anti-inflammatory drug complexes.
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DOI:
10.1039/d2sc04707a
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发表时间:
2023-01-18
期刊:
影响因子:
8.4
通讯作者:
--
中科院分区:
化学1区
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报道了一系列由非甾体抗炎药(NSAIDs)和三苯基膦1-8组成的金(i)配合物的抗乳腺癌干细胞(CSC)特性。最有效的金(i)-非甾体抗炎药复合物1,含有吲哚美辛,对乳腺csc的效力比普通乳腺癌细胞大(高达80倍)。此外,与一组临床使用的乳腺癌药物和一种已建立的抗乳腺CSC药物盐霉素相比,1在更大程度上降低了乳腺球活力。机制研究表明,1诱导的乳腺CSC死亡是由乳腺CSC进入、细胞质定位、细胞内活性氧水平增加、环氧化酶-2下调和抑制以及细胞凋亡引起的。值得注意的是,1在小鼠转移性三阴性乳腺癌模型中也能显著抑制肿瘤生长。据我们所知,1是第一个具有抗乳腺CSC特性的任何几何形状或氧化态的金配合物。报道了一系列由非甾体抗炎药(NSAIDs)和三苯基膦1-8组成的金(i)配合物的抗乳腺癌干细胞(CSC)特性。
The anti-breast cancer stem cell (CSC) properties of a series of gold(i) complexes comprising various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1–8 are reported. The most effective gold(i)-NSAID complex 1, containing indomethacin, exhibits greater potency for breast CSCs than bulk breast cancer cells (up to 80-fold). Furthermore, 1 reduces mammosphere viability to a better extent than a panel of clinically used breast cancer drugs and salinomycin, an established anti-breast CSC agent. Mechanistic studies suggest 1-induced breast CSC death results from breast CSC entry, cytoplasm localisation, an increase in intracellular reactive oxygen species levels, cyclooxygenase-2 downregulation and inhibition, and apoptosis. Remarkably, 1 also significantly inhibits tumour growth in a murine metastatic triple-negative breast cancer model. To the best of our knowledge, 1 is the first gold complex of any geometry or oxidation state to demonstrate anti-breast CSC properties. The anti-breast cancer stem cell (CSC) properties of a series of gold(i) complexes comprising various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1–8 are reported.
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