MURRAY Ana paula
Cativic acid-caffeic acid hybrid exerts cytotoxic effects and induces apoptotic death in human neuroblastoma cells
ALZA, NATALIA P.; MURRAY, ANA P.; SALVADOR, GABRIELA A.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Año: 2017 vol. 390 p. 1229 - 1238
The development of hybrids fromnatural products isa promising strategy for drug discovery. In cancer therapy, thereis a need to discover novel agents that can induce apoptosis incancer cells. To contribute to this field of interest, we investi-gated the effect of a synthetic hybrid from cativic acid andcaffeic acid (5) on viability, proliferation, and apoptosis in hu-man neuroblastoma cells (IMR-32). Three hybrids were pre-pared viaMitsunobu esterification from17-hydroxycativic acid(1) and natural phenols. Cell viability was analyzed by MTTassay. SYTOX green and LDH leakage were used to determinethe cytotoxic effect. Caspase-3 activity, cell cycle phases, andproliferation were analyzed in order to characterize the biolog-ical effects of hybrid 5. The mitogen-activated protein kinase(MAPK) status was evaluated for elucidating the potentialmechanisms involved in hybrid5effect. Hybrid5reduced theviability of IMR-32 cells in a time- and concentration-dependent manner (IC50 = 18.0 ± 1.3μM) as a result of itsantiproliferative effect through changes in the cell cycle distri-bution and induction of apoptosisassociated with activation ofcaspase-3. Exposure to5triggered ERK1/2 activation andnuclear translocation. Hybrid5also promoted an increase innuclear localization of the transcription factor c-Jun. Inhibitionof ERK1/2 and JNK potentiated5-induced inhibition of IMR-32 viability. Hybrid5displays cell growth inhibition by pro-moting cell cycle arrest and apoptosis, through ERK1/2 andJNK participation.