Producción CyT

MEDICINA - IMPACT OF ACYL-COA SYNTHETASE 4 INHIBITOR IN EPITHELIAL OVARIAN CANCER

Congreso

Autoría:

Prada, Jesica G. ; DATTILO, MELINA ANDREA ; Quevedo, Luciano M. ; Orlando, Ulises D. ; Garrido, Maritza P. ; Romero Osses, Carmen ; Podesta, Ernesto J. ; Castillo, Ana F. ; Maloberti, Paula M.

Fecha:

2025

Editorial y Lugar de Edición:

FUNDACION REVISTA MEDICINA

ISSN:

1669-9106

Resumen *

Acyl-CoA synthetase 4 (ACSL4) in an enzyme that plays a significant role in arachidonic acid metabolism. It has been involved in pathological processes, including prostate, liver, and breast cancer. We have previously developed and characterized an inhibitor of ACSL4, PRGL493. We aimed to examine the effect of the ACSL4 inhibitor in epithelial ovarian cancer (EOC). Ovarian cancer is the third most prevalent gynecological malignancy and the leading cause of mortality within this category. Our previous research showed significantly higher ACSL4 levels in EOC patient samples relative to normal tissue. Western blot analysis revealed elevated levels of ACSL4 in the EOC lines A2780, OV-90, and SKOV-3 compared to non-tumorigenic HOSE cells. The PRGL493 inhibitor significantly reduced cell proliferation in EOC cells. Here we investigated the inhibitor’s impact on cell migration, ABC transporters activity and tumor sphere formation. PRGL493-treated SKOV-3 cells showed significantly slower wound closure after 20 hours compared to controls(p < 0.05). Efflux assays showed higher accumulation of doxorubicin and Hoechst in PRGL493-treated cells compared to controls, indicating lower transporter’s activity. PRGL493 also impaired tumor sphere formation in SKOV-3 cells. We then tested the combination of PRGL493 with chemotherapeutic drugs on SKOV-3 cells. After 96 hours of treatment with suboptimal doses of carboplatin (1 mg/ml), paclitaxel (0.15 nM), and doxorubicin (0.027 μM), alone or with PRGL493 (10 μM), cell viability was assessed via MTT assay. The combination of the drugs with PGRL493 enhanced the inhibition of cell proliferation. The results show that ACSL4 inhibition has an impactin cell migration, ABC transporter activity and sensitizes SKOV-3 cells to chemotherapeutic treatment. Información suministrada por el agente en SIGEVA

Palabras Clave

ACSL4SKOV-3Ovarian CancerPRGL493