Novel Suicide Ligands of Tubulin Arrest Cancer Cells in S-Phase
| Autor: | Imre Weisz, Yue Wang, J. George Bekesi, Yi-He Ling, Ashley Davis, Kim Middleton, Jian-Dong Jiang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Cell division Antineoplastic Agents macromolecular substances Ligands lcsh:RC254-282 S Phase Tumor Cells Cultured medicine Humans anti-tumor Mitosis anti-cancer biology novel Ligand Chemistry apoptosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tubulin Mechanism of action Biochemistry tubulin Apoptosis Cancer cell biology.protein Phosphorylation medicine.symptom Research Article |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 1, Iss 6, Pp 498-507 (1999) |
| ISSN: | 1522-8002 1476-5586 |
| Popis: | It is presently accepted that the mechanism of action for all anti-tumor tubulin ligands involves the perturbation of microtubule dynamics during the G2/M phase of cell division and subsequent entry into apoptosis 1]. In this report, we challenge the established dogma by describing a unique mechanism of action caused by a novel series of tubulin ligands, halogenated derivatives of acetamido benzoyl ethyl ester. We have developed a suicide ligand for tubulin, which covalently attaches to the target and shows potent cancericidal activity in tissue culture assays and in animal tumor models. These compounds target early S-phase at the G1/S transition rather than the G2/M phase and mitotic arrest. Bcl-2 phosphorylation, a marker of mitotic microtubule inhibition by other tubulin ligands was dramatically altered, phosphorylation was rapid and biphasic rather than a slow linear event. The halogenated ethyl ester series of derivatives thus constitute a unique set of tubulin ligands which induce a novel mechanism of apoptosis. |
| Databáze: | OpenAIRE |
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