id_1045. ANTI-APOPTOTIC POTENTIAL OF CLASSICAL AND NOVEL ANTI-INFLAMMATORY COMPOUNDS – IN VITRO STUDY IN HUMAN NEUROBLASTOMA SH-SY5Y CELLS
Danuta Jantas1, Aleksandra Mąsior1, Piotr Chmielarz1, Ryszard Bugno2, Grzegorz Kreiner1
1 Maj Institute of Pharmacology Polish Academy of Sciences, Department of Brain Biochemistry, Smętna 12 Str, 31-343 Kraków, Poland
2 Maj Institute of Pharmacology Polish Academy of Sciences, Department of Medicinal Chemistry, Smętna 12 Str, 31-343 Kraków, Poland
INTRODUCTION: MIP001 is novel anti-inflammatory and analgesic drug with favourable safety profile even at high doses. In our previous studies we showed a neuroprotective potential of MIP001. This compound, but not classical anti-inflammatory agent ibuprofen (Ibu), showed a higher protective efficacy in apoptotic (MPP+), than oxidative stress-based (H2O2 and 6-OHDA) neuronal cell damage models.
AIM(S): In order to further investigate neuroprotective potency of MIP001 in comparison to the effect of Ibu, we employed two models of apoptosis: i) based on activation of intracellular (staurosporine, St) and ii) extracellular (doxorubicin, Dox) apoptotic pathways in undifferentiated (UN-) and retinoic acid (RA)-differentiated SH-SY5Y cells.
METHOD(S): The neuroprotective effects were measured by biochemical assays (MTT reduction and LDH release assays), microscopic imaging and evaluation of apoptosis (caspase-3 activity) and necrosis (propidium iodide staining, PI) markers.
RESULTS: We demonstrated that MIP001 (at concentrations 10-100 microM) but not Ibu partially attenuated the cell damage induced by Dox and this effect was observed only in RA-SH-SY5Y cells. However this was not associated with attenuation of caspase-3 activity nor lowering of the number of necrotic cells. We did not find any protection of MIP001 and Ibu against cell damage induced by St in both studied cell phenotypes.
CONCLUSIONS: Our results evidenced a neuroprotective potential of MIP001 in neuronally differentiated SH-SY5Y cells against apoptotic cell damage induced extracellularly probably via inhibition of caspase-3 independent mechanisms, which need further investigation.
FINANCIAL SUPPORT: The study was supported by a programme coordinated by the Medical Research Agency, co-financed by the European Union under the NextGeneration EU initiative, within the framework of the National Recovery Plan, Component D, Investment D3.1.1 (project no. 2024/ABM/03/KPO/KPOD.07.07-IW.07-0173/24-00).