Mariam Fathy, Salwa M El-Hallouty, Ahmed S Mansour, Mohamed Fahmy, Nourhan Hassan, Emad M ElZayat
{"title":"The Anti-proliferative Effect, Apoptotic Induction, and Cell Cycle Arrest of Tetra Halo Ruthenate Nanocomposites in Different Human Cancer Cell Lines.","authors":"Mariam Fathy, Salwa M El-Hallouty, Ahmed S Mansour, Mohamed Fahmy, Nourhan Hassan, Emad M ElZayat","doi":"10.1007/s12013-024-01519-y","DOIUrl":null,"url":null,"abstract":"<p><p>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 IC<sub>50</sub> 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 IC<sub>50</sub> 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.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biochemistry and Biophysics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12013-024-01519-y","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.