title: New derivative of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-one (BChTT) elicits antiproliferative effect via p38-mediated cell cycle arrest in cancer cells.
abstract: 2-(2,4-Dihydroxyphenyl)thieno-1,3-thiazin-4-ones are a group of new compounds with potential anticancer activity. This type of derivatives was poorly investigated in the area of synthesis and biological activities. In the present study the antiproliferative action of the most active derivative BChTT was described. The aim of biological evaluation was to investigate the ability of the compound to inhibit cancer cell proliferation and identify mechanism involved in its action on the molecular level. BChTT inhibited the proliferation of lung cancer A549, colon cancer HT-29 and glioma C6 cells in the concentration-dependent manner. It was not toxic to normal cells including skin fibroblasts, hepatocytes and oligodendrocytes in the antiproliferative concentrations. BChTT decreased the DNA synthesis in the treated cancer cells and induced cell cycle arrest in the G0/G1 phase. Moreover, the ability of the compound to activate p38 kinase and decrease cyclin D1 expression was estimated. Participation of p38 kinase in the antiproliferative action of the compound was confirmed by the analysis of BChTT activity in the cells with the p38 silenced gene. The obtained results may suggest the ability of the tested derivative to inhibit cancer cells proliferation by induction of p38-mediated cyclin D1 downregulation.
authors.affiliation: Department of Medical Biology, Institute of Rural Health, Lublin, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Juszczak
authors.affiliation: Department of Pharmacology, Medical University, Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Walczak
authors.affiliation: Department of Chemistry, University of Life Sciences, Lublin, Poland. Electronic address: joanna.matysiak@up.lublin.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Department of Medical Biology, Institute of Rural Health, Lublin, Poland.
authors.forename: Marta K
authors.initials: MK
authors.lastname: Lemieszek
authors.affiliation: Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Pharmacology, Medical University, Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Langner
authors.affiliation: Institute of Industrial Organic Chemistry, Warsaw, Poland.
authors.forename: Monika M
authors.initials: MM
authors.lastname: Karpińska
authors.affiliation: Department of Clinical Immunology, Medical University, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Pożarowski
authors.affiliation: Department of Chemistry, University of Life Sciences, Lublin, Poland; Institute of Industrial Organic Chemistry, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niewiadomy
authors.affiliation: Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C000611887:2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-one; D000970:Antineoplastic Agents; D013843:Thiazines; D013876:Thiophenes; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 2-(2,4-Dihydroxyphenyl)thieno-1,3-thiazin-4-one; Antiproliferative action; Cell cycle arrest; Cyclin D1; p38 kinase