A new platinum complex of triazine demonstrates G1 arrest with novel biological profile in human breast cancer cell line, MDA-MB-468
| Autor: | Jon G. Church, Soma Mandal, Vernon J. Richardson, Sanat K. Mandal, Saroj K. Pramanik, John N. Bridson, Gervais Bérubé, Tram N. Q. Pham, Eric Asselin |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Apoptosis Breast Neoplasms Biochemistry Structure-Activity Relationship chemistry.chemical_compound Superoxide Dismutase-1 Cell Line Tumor Drug Discovery Organometallic Compounds medicine Animals Humans Computer Simulation Cytotoxicity Molecular Biology Platinum Triazine Cisplatin MDA-MB-468 Superoxide Dismutase Triazines Chemistry Organic Chemistry G1 Phase Cell cycle Molecular biology In vitro Molecular Medicine Platinum Compound Cattle Female Drug Screening Assays Antitumor Tumor Suppressor Protein p53 Protein Binding medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 17:2139-2145 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2007.01.116 |
| Popis: | A novel class of platinum(II) complexes of pyridine sulfide derivatives of triazine was synthesized, characterized, and investigated using the human breast cancer cell line, MDA-MB-468. S-30 was one of the most potent derivatives of its class (IC(50), 0.39 microM) eliciting the greatest biological response. S-30 induced arrest in the G1 phase and apoptosis (TUNEL assay) in a p53/p21(WAF1/CIP1)-consistent manner. Modeling and docking experiments were performed for three known targets for cisplatin, d(GpG), d(ApG), and a protein (Cu/Zn superoxide dismutase, SOD) from bovine origin. A Blast search of bovine SOD was performed to identify analogous human protein targets resulting in about 22 human proteins. A multi-sequence alignment of those targets showed80% sequence identity and88% similarity. One of them is SOD1 that is differentially expressed (based on global gene expression pattern) in various forms of cancer and other diseases. SOD1 controls apoptosis via p53/BAD/BAX/BCL2 in the amyotrophic lateral sclerosis (ALS) pathway and is also involved in various other KEGG's pathways. Results suggest that the S-30 is a potential cytotoxic agent. |
| Databáze: | OpenAIRE |
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