Cytostatic/Cytotoxic Effects of 5-Fluorouridine Nucleolipids on Colon, Hepatocellular, and Renal Carcinoma Cells: in vitro Identification of a Potential Cytotoxic Multi-Anticancer Drug
| Autor: | Jürgen Schmitt, Anisa Farhat, Gabriel A. Bonaterra, Doris Röthlein, Ralf Kinscherf, Martin Wolf, Helmut Rosemeyer, Edith Malecki |
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| Rok vydání: | 2014 |
| Předmět: |
Drug
Cell Survival media_common.quotation_subject Cell Antineoplastic Agents Bioengineering Pharmacology Biochemistry Cell Line Tumor medicine Humans Cytotoxic T cell 5 fluorouridine RNA Messenger Cytotoxicity Uridine Molecular Biology Incubation media_common Caspase 3 Chemistry Hep G2 Cells General Chemistry General Medicine In vitro medicine.anatomical_structure Apoptosis Molecular Medicine Tumor Suppressor Protein p53 HT29 Cells |
| Zdroj: | Chemistry & Biodiversity. 11:469-482 |
| ISSN: | 1612-1872 |
| Popis: | The insufficient penetration through the cell membranes is one of the major drawbacks of chemotherapeutics such as 5-fluorouracil (5-FU; 1). To improve the penetration, a useful strategy is the attachment of lipophilic moieties. Thus, we have synthesized a series of nucleolipid derivatives of 5-fluorouridine (5-FUrd; 2a), carrying lipophilic moieties at N(3) and/or at the 2',3'-O position, i.e., 3a, 3b, 4-7, and tested their cytostatic/cytotoxic activities towards three carcinoma cell lines (colon (HT-29), hepatocellular (HepG2), and renal (RENCA)) in comparison with 5-FU (1) and 5-FUrd (2a). After 48 h of incubation, four derivatives, 3a, 3b, 5, and 7, showed inhibitory effects on the survival of HT-29, HepG2, and RENCA cells. Additionally, to differentiate between anticancer and side-effects, we tested the cytotoxicity of the derivatives in human macrophages. Interestingly, the derivatives 4, 5, and 6 did not exhibit any effects on survival of THP-1 macrophages. Furthermore, we investigated the apoptosis induction of compound 1 and 2a, and the above-mentioned derivatives in HT-29 cells. Derivative 5 showed the highest significant (p |
| Databáze: | OpenAIRE |
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