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A new platinum complex of triazine demonstrates G1 arrest with novel biological profile in human breast cancer cell line, MDA-MB-468.
Mandal, Soma; Bérubé, Gervais; Asselin, Eric; Richardson, Vernon J; Church, Jon G; Bridson, John; Pham, Tram N Q; Pramanik, Saroj K; Mandal, Sanat K.
Afiliação
  • Mandal S; Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Bioorg Med Chem Lett ; 17(8): 2139-45, 2007 Apr 15.
Article em En | MEDLINE | ID: mdl-17321743
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 showed >80% sequence identity and >88% 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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Platina / Triazinas / Neoplasias da Mama / Fase G1 / Antineoplásicos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Platina / Triazinas / Neoplasias da Mama / Fase G1 / Antineoplásicos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article