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影响肿瘤细胞中Prominin-1/CD133表达及干细胞因子释放的新型钯(II)配合物

Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells.

作者信息

Fischer-Fodor Eva, Mikláš Roman, Rišiaňová Lucia, Cenariu Mihai, Grosu Ioana-Georgeta, Virag Piroska, Perde-Schrepler Maria, Tomuleasa Ciprian, Berindan-Neagoe Ioana, Devínsky Ferdinand, Miklášová Natalia

机构信息

"I. Chiricuta" Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania.

Medfuture Research Center for Advanced Medicine "Iuliu Hatieganu", University of Medicine and Pharmacy, Babes 8, RO-400012 Cluj-Napoca, Romania.

出版信息

Molecules. 2017 Mar 30;22(4):561. doi: 10.3390/molecules22040561.

Abstract

New Pd(II) complexes of 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. The complexes were tested in vitro on human colon and hepatic carcinoma cell lines, normal hepatic cells and hematopoietic progenitor cells. Biological tests proved that Pd(II) complexes and (containing a curcumin derivative) exhibit a strong in vitro antitumor effect against the cells derived from human colorectal carcinoma and the hepatic metastasis of a colorectal carcinoma. Complex has an outstanding inhibitory effect against BRAF-mutant colon carcinoma and hepatocarcinoma cell growth; and are both more active than the free ligand and have the capacity to trigger early apoptotic processes. By flow cytometric measurements, an important decrease of prominin-1 (CD133) molecule expression on tumor cells membrane was identified in cell populations subjected to and . Quantitative immune enzymatic assay proved restrictions in stem cell factor (SCF) release by treated tumor cells. Although less cytotoxic, the free ligand inhibits the surface marker CD133 expression in hepatocarcinoma cells, and in HT-29 colon carcinoma. The new synthesized Pd(II) complexes and exhibit an important potential through their selective cytotoxic activity and by targeting the stem-like tumor cell populations, which leads to the tumor growth arrest and prevention of metastasis.

摘要

合成了1,7 - 双(2 - 甲氧基苯基)庚 - 1,6 - 二烯 - 3,5 - 二酮的新型钯(II)配合物并对其进行了结构表征。这些配合物在体外对人结肠和肝癌细胞系、正常肝细胞及造血祖细胞进行了测试。生物学测试证明,钯(II)配合物 和 (含有姜黄素衍生物)对源自人结肠直肠癌和结肠直肠癌肝转移的细胞表现出强大的体外抗肿瘤作用。配合物 对BRAF突变型结肠癌和肝癌细胞生长具有显著的抑制作用; 和 均比游离配体更具活性,并有能力触发早期凋亡过程。通过流式细胞术测量,在接受 和 处理的细胞群体中,肿瘤细胞膜上的prominin - 1(CD133)分子表达显著降低。定量免疫酶测定证明经处理的肿瘤细胞释放干细胞因子(SCF)受到限制。尽管细胞毒性较小,但游离配体可抑制肝癌细胞和HT - 29结肠癌细胞表面标志物CD133的表达。新合成的钯(II)配合物 和 通过其选择性细胞毒性活性以及靶向肿瘤干细胞样细胞群体,展现出重要的潜力,这导致肿瘤生长停滞并预防转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae5a/6154565/a17677abce3b/molecules-22-00561-sch001.jpg

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