Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition
| Autor: | Dewi Safitri, David S. Bailey, Graham Ladds, Maksym V. Kopanitsa, Liliya Kopanitsa |
|---|---|
| Přispěvatelé: | Kopanitsa, Liliya [0000-0002-3752-2887], Ladds, Graham [0000-0001-7320-9612], Bailey, David S [0000-0002-9343-3408], Apollo - University of Cambridge Repository, Bailey, David S. [0000-0002-9343-3408] |
| Rok vydání: | 2021 |
| Předmět: |
Combination therapy
QH301-705.5 Cell Survival Phosphodiesterase Inhibitors proliferation Phosphodiesterase 3 multidrug resistance-associated protein 1 drug combination Antineoplastic Agents Catalysis Article Inorganic Chemistry chemistry.chemical_compound Cell Line Tumor Cyclic AMP Humans Biology (General) Physical and Theoretical Chemistry Phosphodiesterase inhibitor QD1-999 Molecular Biology Cyclic GMP Spectroscopy Cell Proliferation Phosphoric Diester Hydrolases Organic Chemistry Trequinsin glioblastoma Phosphodiesterase Drug Synergism General Medicine Computer Science Applications Chemistry chemistry Toxicity Cancer research Quinolines Pyrazoles Multidrug Resistance-Associated Protein 1 PDE10A Multidrug Resistance-Associated Proteins phosphodiesterase inhibitor |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 9665, p 9665 (2021) Volume 22 Issue 18 |
| DOI: | 10.17863/cam.75257 |
| Popis: | The paucity of currently available therapies for glioblastoma multiforme requires novel approaches to the treatment of this brain tumour. Disrupting cyclic nucleotide-signalling through phosphodiesterase (PDE) inhibition may be a promising way of suppressing glioblastoma growth. Here, we examined the effects of 28 PDE inhibitors, covering all the major PDE classes, on the proliferation of the human U87MG, A172 and T98G glioblastoma cells. The PDE10A inhibitors PF-2545920, PQ10 and papaverine, the PDE3/4 inhibitor trequinsin and the putative PDE5 inhibitor MY-5445 potently decreased glioblastoma cell proliferation. The synergistic suppression of glioblastoma cell proliferation was achieved by combining PF-2545920 and MY-5445. Furthermore, a co-incubation with drugs that block the activity of the multidrug resistance-associated protein 1 (MRP1) augmented these effects. In particular, a combination comprising the MRP1 inhibitor reversan, PF-2545920 and MY-5445, all at low micromolar concentrations, afforded nearly complete inhibition of glioblastoma cell growth. Thus, the potent suppression of glioblastoma cell viability may be achieved by combining MRP1 inhibitors with PDE inhibitors at a lower toxicity than that of the standard chemotherapeutic agents, thereby providing a new combination therapy for this challenging malignancy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|