Original research paper. Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties
| Autor: | Lulzime, Ballazhi, Faik, Imeri, Ahmed, Jashari, Emil, Popovski, Goran, Stojković, Aleksandar J, Dimovski, Bozhana, Mikhova, Kristina, Mladenovska |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Dose-Response Relationship
Drug Molecular Structure Antineoplastic Agents Apoptosis Breast Neoplasms Drug Synergism Permeability G2 Phase Cell Cycle Checkpoints Inhibitory Concentration 50 Structure-Activity Relationship Solubility Cell Movement Coumarins Doxorubicin Drug Design Antineoplastic Combined Chemotherapy Protocols MCF-7 Cells Humans Female Phosphorylation Proto-Oncogene Proteins c-akt Cell Proliferation Signal Transduction |
| Zdroj: | Acta pharmaceutica (Zagreb, Croatia). 67(1) |
| ISSN: | 1846-9558 |
| Popis: | This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski's rule of five for good permeability (absorption) potential. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|