基于吡啶碱的钯和铂络合物通过癌细胞中的凋亡蛋白信号诱导抗癌效果。

IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mohamed M. El-bendary, Abdullah Akhdhar, Abdullah S. Al-Bogami, Doaa Domyati, Abdulaziz A. Kalantan, Faisal Ay Alzahrani, Samer M. Alamoudi, Ryan A. Sheikh, Ehab M. M. Ali
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引用次数: 0

摘要

钯和铂络合物,尤其是含有顺铂的络合物,可以成为有用的化疗药物。含有吡啶碱的络合物可以提供不良反应较少、治疗剂量较低的替代品。铂(SCN)2(4-Acpy)2] (1)、[钯(N3)2(4-Acpy)2] (2)、[钯(paOH)2].2Cl (3) 和 [铂(SCN)2(paO)2] (4) 复合物是在常温下通过自组装方法制备的;(4-Acpy = 4-乙酰基吡啶,paOH = 吡啶-2-甲醛肟)。利用光谱和 X 射线晶体学方法确认了 1-4 号配合物的结构。1-4 号配合物具有相似的同分异构特征,包括吡啶配体与钯或铂离子的反式配位几何。配合物 1-4 的三维网络结构是由无数个离散的单核分子通过 H 键延伸而成的。研究人员在 MCF-7、T47D 乳腺癌细胞和 HCT116 结肠癌细胞上评估了带有吡啶配体的钯和铂复合物 1-4。研究评估了 MCF-7 细胞在钯或铂与吡啶碱结合处理后通过细胞凋亡和细胞周期阶段死亡的情况。用这些复合物处理 MCF-7 细胞后,对细胞凋亡信号(Bcl2、p53、Bax 和 c-Myc)和细胞周期信号(p16、CDK1A、CDK1B)的表达进行了评估。与其他复合物和顺铂相比,复合物 1 在 MCF-7 细胞中的 IC50 最低,复合物 2 在 T47D 细胞中的 IC50 最低。复合物 4 对 HCT116 的有效性最高。复合物 1-4 对所有癌细胞系的选择性指数(SI)均大于 2,这表明复合物在相同剂量下对正常细胞的毒性较低。用复合物 2 和铂复合物 4 处理的 MCF-7 细胞表现出最高水平的早期凋亡。用四种复合物 1-4 和顺铂处理过的细胞中,c-Myc 的高表达可诱导 p53。所有复合物 1-4 都能提高 Bax 的表达,并触发肿瘤抑制基因 p53。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells

Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells

Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1–4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1–4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1–4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1–4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1–4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1–4 and cisplatin could induce p53. All complexes 1–4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.

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来源期刊
Biometals
Biometals 生物-生化与分子生物学
CiteScore
5.90
自引率
8.60%
发文量
111
审稿时长
3 months
期刊介绍: BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of: - metal ions - metal chelates, - siderophores, - metal-containing proteins - biominerals in all biosystems. - BioMetals rapidly publishes original articles and reviews. BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.
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