P53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells
| Autor: | Mirella Rambaldi, Concettina Cappadone, Alessandra Graziadio, Emil Malucelli, Lorenzo Montanaro, Claudio Stefanelli, Giovanna Farruggia, Lucia Merolle, Carmine Onofrillo, Maddalena Zini, Alessandra Locatelli, Azzurra Sargenti, Stefano Iotti |
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| Přispěvatelé: | Cappadone, C, Stefanelli, C., Malucelli, E., Zini, M., Onofrillo, C., Locatelli, A., Rambaldi, M., Sargenti, A., Merolle, L., Farruggia, G., Graziadio, A., Montanaro, L., Iotti, S. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
p53
Cyclin-Dependent Kinase Inhibitor p21 Indoles Cell cycle checkpoint medicine.medical_treatment Biophysics Gene Expression Antineoplastic Agents Apoptosis Biology Biochemistry Antineoplastic Agent U2OS Cell Cycle Checkpoint Cell Line Tumor medicine Humans SaOS2 RNA Small Interfering Molecular Biology Cell Proliferation Chemotherapy Osteosarcoma Osteoblasts Cell growth Osteoblast Medicine (all) Apoptosi Cell Cycle Checkpoints Cell Biology Cell cycle medicine.disease Alkaline Phosphatase Cell biology Thiazoles Biophysic Cell culture Indole Alkaline phosphatase Indole derivative Thiazole Tumor Suppressor Protein p53 Human |
| Popis: | Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. |
| Databáze: | OpenAIRE |
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