The Anti-proliferative Effect, Apoptotic Induction, and Cell Cycle Arrest of Tetra Halo Ruthenate Nanocomposites in Different Human Cancer Cell Lines.

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mariam Fathy, Salwa M El-Hallouty, Ahmed S Mansour, Mohamed Fahmy, Nourhan Hassan, Emad M ElZayat
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Abstract

Chemotherapy is the most common cancer treatment, and metallic anticancer compounds have generated increasing amounts of interest since the discovery of cisplatin. More recently, scientists have focused on ruthenium-based compounds as alternatives for platinum compounds, which seem like ideal therapeutic anticancer alternatives to platinum derivatives. The present study aims to assess whether one or more of three Ruthenium-based nanocomposites, namely Ru+Lysine+CTAB (RCTL), Ru+CTAB (RCT), and Ru+Lysine (RL) exhibit pronounced anti-proliferative properties against different cancer cells. Three Ruthenium nanocomposites have been synthesized by standard chemical methods and characterized by Dynamic light scattering (DLS) and Transmission electron microscopy (TEM). The cytotoxic effect of the three composites has been evaluated by MTT in-vitro assay for different human cancer cell lines, namely MCF7, HepG2, A549, and PC3 versus normal human skin cell line (BJ1). The molecular underlying mechanisms of cytotoxicity have been assessed via qRT-PCR for pro-apoptotic makers P53 and Casp-3, and anti-apoptotic marker Bcl-2 as well as flow cytometric analysis of the cell cycle. Among the 3 nanocomposites, RCTL gave the best sensitivity and cytotoxicity especially on HepG2 with IC50 0.55 µg/ml but was still toxic on normal cell line with dose <12.5 µg/ml. RCTL and RCT nanocomposites have demonstrated a significant increase in the expression of P53 and Casp-3 markers versus untreated controls, but a significant reduction in the expression of Bcl-2. There was a direct correlation between the cytotoxic effect and the degree of apoptosis in the different cancer cell lines. The present study has also proved cell cycle arrest at G2-M and pre-G1 phases under the effect of IC50 of RCTL and RCT nanocomposites in different cancer lines with the best effect being achieved in HepG2 cells. Ruthenium nanocomposites seem to open a new avenue in cancer therapy.

四卤钌酸盐纳米复合材料在不同人类癌症细胞株中的抗增殖作用、凋亡诱导和细胞周期停滞。
化疗是最常见的癌症治疗方法,自顺铂被发现以来,金属抗癌化合物引起了越来越多的关注。最近,科学家们把目光投向了钌基化合物,认为它们是铂化合物的理想治疗性抗癌替代品。本研究旨在评估三种钌基纳米复合材料,即 Ru+赖氨酸+CTAB(RCTL)、Ru+CTAB(RCT)和 Ru+赖氨酸(RL)中的一种或多种是否对不同的癌细胞具有明显的抗增殖特性。我们采用标准化学方法合成了三种钌纳米复合材料,并通过动态光散射(DLS)和透射电子显微镜(TEM)对其进行了表征。通过 MTT 体外实验评估了三种复合材料对不同人类癌症细胞株(即 MCF7、HepG2、A549 和 PC3)和正常人类皮肤细胞株(BJ1)的细胞毒性作用。通过 qRT-PCR 检测促凋亡分子 P53 和 Casp-3、抗凋亡分子 Bcl-2 以及细胞周期的流式细胞分析,评估了细胞毒性的分子基础机制。在这三种纳米复合材料中,RCTL 的灵敏度和细胞毒性最高,尤其是对 HepG2 的 IC50 为 0.55 µg/ml,但对正常细胞株仍有毒性,RCTL 和 RCT 纳米复合材料在不同癌细胞株中的剂量为 50,对 HepG2 细胞的效果最好。钌纳米复合材料似乎为癌症治疗开辟了一条新途径。
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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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