Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.
Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.
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具有良好抗癌活性的铂 (IV)-金 (I) 药物：2D 和 3D 三阴性乳腺癌模型的精选研究。
DOI：
10.1002/chem.202302045
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Contel,Maria
中科院分区：
文献类型：
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作者：
López-Hernández,JavierE;Nayeem,Nazia;Cerón-Carrasco,JoséP;Ahad,Afruja;Hafeez,Aiman;León,IgnacioE;Contel,Maria
本文报道了一类新的双核和三核铂(IV)-金(I)异金属化合物[Pt(L)nCl2(OH){(OOC-4-C6H4-PPh2)AuCl}x](L=NH_3，n=2；x=1，2；L=环己二胺，n=1；x=2)。这些化合物对一小部分肾、膀胱、卵巢和乳腺癌细胞株具有细胞毒性和选择性。我们选择了一个基于奥沙利铂的含有PtIVcore的三核PtAu2化合物，进一步研究了它的细胞死亡途径、细胞和细胞器摄取以及对三阴性乳腺癌mda-MB-231 细胞的抗癌作用。这种化合物诱导细胞凋亡，并主要聚集在细胞核和线粒体中。它还表现出显著的抗迁移和抗血管生成特性，并对TNBC 3D球体具有强大的细胞毒作用。即使在还原剂存在下，三核化合物似乎也不与小牛胸腺(CT)DNA和质粒(PBR322)发生相应的相互作用，但对TNBC细胞中促血管生成酶硫氧还蛋白还原酶(TrxR)具有抑制作用。
New heterometallic binuclear and trinuclear platinum(IV)–gold(I) compounds of the type [Pt(L)nCl2(OH){(OOC‐4‐C6H4‐PPh2)AuCl}x] (L=NH3,n=2;x=1, 2; L=diaminocyclohexane, DACH,n=1;x=2) are described. These compounds are cytotoxic and selective against a small panel of renal, bladder, ovarian, and breast cancer cell lines. We selected a trinuclear PtAu2compound containing the PtIVcore based on oxaliplatin, to further investigate its cell‐death pathway, cell and organelle uptake and anticancer effects against the triple‐negative breast cancer (TNBC) MDA‐MB‐231 cell line. This compound induces apoptosis and accumulates mainly in the nucleus and mitochondria. It also exerts remarkable antimigratory and antiangiogenic properties, and has a potent cytotoxic effect against TNBC 3D spheroids. Trinuclear compounds do not seem to display relevant interactions with calf thymus (CT) DNA and plasmid (pBR322) even in the presence of reducing agents, but inhibit pro‐angiogenic enzyme thioredoxin reductase (TrxR) in TNBC cells.