Molecular interaction of a kinase inhibitor midostaurin with anticancer drug targets, S100A8 and EGFR: transcriptional profiling and molecular docking study for kidney cancer therapeutics

The S100A8 and epidermal growth factor receptor (EGFR) proteins are proto-oncogenes that are strongly expressed in a number of cancer types. EGFR promotes cellular proliferation, differentiation, migration and survival by activating molecular pathways. Involvement of proinflammatory S100A8 in tumor...

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Bibliographic Details
Published in:PloS one 2015-03, Vol.10 (3), p.e0119765
Main Authors: Mirza, Zeenat, Schulten, Hans-Juergen, Farsi, Hasan Ma, Al-Maghrabi, Jaudah A, Gari, Mamdooh A, Chaudhary, Adeel Ga, Abuzenadah, Adel M, Al-Qahtani, Mohammed H, Karim, Sajjad
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic agents
Antineoplastic drugs
Antitumor agents
Arteriosclerosis
Atherosclerosis
Biomarkers
Calgranulin A - biosynthesis
Calgranulin A - chemistry
Calgranulin A - genetics
Cancer
Cancer research
Cancer therapies
Cell cycle
Cell differentiation
Cell growth
Cell Proliferation - drug effects
Cell survival
Cytology
Deoxyribonucleic acid
Development and progression
Differentiation (biology)
DNA
DNA repair
Drug Discovery
Drug Resistance, Neoplasm - drug effects
Drugs
Enzyme inhibitors
Epidermal growth factor
Epidermal growth factor receptors
Extravasation
Female
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Genes
Health aspects
Hospitals
Humans
Inflammation
Inhibitors
Interleukin 12
Ionizing radiation
Kidney cancer
Kidney Neoplasms - drug therapy
Kidney Neoplasms - genetics
Kidney Neoplasms - pathology
Kinases
Leukocyte migration
Leukocytes
Lung cancer
Male
Medical research
Medicine
Metastasis
Middle Aged
Molecular docking
Molecular Docking Simulation
Molecular modelling
Molecular Targeted Therapy
Mutation
Notch protein
Pathology
Protein Conformation - drug effects
Protein Kinase Inhibitors - administration & dosage
Proteins
Proto-oncogenes
R&D
Receptor, Epidermal Growth Factor - biosynthesis
Receptor, Epidermal Growth Factor - chemistry
Receptor, Epidermal Growth Factor - genetics
Research & development
Signal transduction
Signal Transduction - drug effects
Signaling
Staurosporine - administration & dosage
Staurosporine - analogs & derivatives
Survival
Transcription
Transcription (Genetics)
Tumors
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Summary:The S100A8 and epidermal growth factor receptor (EGFR) proteins are proto-oncogenes that are strongly expressed in a number of cancer types. EGFR promotes cellular proliferation, differentiation, migration and survival by activating molecular pathways. Involvement of proinflammatory S100A8 in tumor cell differentiation and progression is largely unclear and not studied in kidney cancer (KC). S100A8 and EGFR are potential therapeutic biomarkers and anticancer drug targets for KC. In this study, we explored molecular mechanisms of interaction profiles of both molecules with potential anticancer drugs. We undertook transcriptional profiling in Saudi KCs using Affymetrix HuGene 1.0 ST arrays. We identified 1478 significantly expressed genes, including S100A8 and EGFR overexpression, using cut-off p value
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0119765