Oğuzhan Karaosmanoğlu, Halil Berber, Hülya Sivas, Ulku Dilek Uysal
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引用次数: 0
Abstract
Chemotherapy resistance is a major obstacle in cancer; thus, the development of new anticancer agents is being studied with great importance. Schiff bases containing an azomethine group have been widely used in various pharmaceutical applications. Here, five Schiff base derivatives of 2-hydroxybenzaldehyde (8S1-8S5) were synthesized and characterized. Their cytotoxicity was screened against six cancerous and two normal cell lines using a neutral red uptake assay. The apoptotic mechanism of the compound 8S3 in MCF-7 cells was evaluated through a combination of cell cycle analysis, measurement of mitochondrial membrane potential, reactive oxygen species levels, caspase activity, analysis of gene expression in the mitogen-activated protein kinase (MAPK) signalling pathway, and in silico analysis studies. Treatment of the cells with 8S3 resulted in an increase in sub-G0/G1 populations and MMP disruption. The expressions of 30 genes involved in MAPK signalling were upregulated, while 10 genes were downregulated in these cells. This transcriptional profile supports a MAPK-mediated apoptotic response and highlights 8S3's potential to overcome chemoresistance by disrupting key survival MAPK signalling pathways. 8S3 might induces apoptosis through a mechanism involving modulation of MAPK pathway and mitochondrial dysfunction, in a ROS-independent manner. Results highlight 8S3's potential as a candidate for further development of anti-cancer drugs 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.
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