[en] Epithelial ovarian cancer, which accounts for about 90% of primary ovarian tumours, is the most lethal of gynaecological cancers due to the non-specific symptoms in the initial stages of the disease. With the current therapeutic options, the results obtained are not satisfactory and it is necessary to study other alternatives. Ovarian cancer cells have altered iron metabolism so that iron accumulates intracellularly, making them susceptible to ferroptosis. Ferroptosis is a type of non-apoptotic regulated cell death triggered by iron-dependent lipid peroxidation. Therefore, the use of ferroptosis modulators (erastin, RSL3, DFO and ferrostatin-1) could become an alternative tool in the treatment of this type of cancer. In this study, ovarian cancer cells (OVCA) were treated with different compounds that modulate ferroptosis to analyse their effect on proliferation capacity. In addition, recipient OVCAs were treated with the conditioned medium obtained from donor OVCAs treated with the different ferroptosis modulators to assess whether the ferroptotic cells can propagate the process in a paracrine manner. Of the two inducers used, RSL3 was able to decrease the proliferation of OVCAs, while erastin did not alter the proliferative capacity of the cells. Contrary to expectations, the inhibitor DFO affected cell proliferation, specifically by decreasing it. In contrast, ferrostatin-1 did not seem to alter cell proliferation. Likewise, the conditioned medium of RSL3-treated OVCAs was able to decrease proliferation in OVCAs. Ferroptosis has become a promising tool for the treatment of cancer and specifically for the management of epithelial ovarian cancer using pharmacological modulators of the process.

[gl] O cancro de ovario epitelial, que representa preto do 90% dos tumores de ovario primarios, é o máis letal dos cancros xinecolóxicos debido aos síntomas inespecíficos nas fases iniciais da enfermidade. Coas opcións terapéuticas actuáis, os resultados obtidos non son satisfactorios, sendo necesario estudar outras alternativas. As células cancerosas de ovario presentan alterado o metabolismo do ferro de forma que se produce a acumulación intracelular de ferro. A ferroptose é un tipo de morte celular regulada non apoptótica desencadeada pola peroxidación lipídica dependente do ferro. É por isto que o uso de moduladores de ferroptose (erastina, RSL3, DFO y ferrostatina-1), poderían converterse nunha alternativa no tratamento deste tipo de cancro. Neste traballo, as células canceríxenas de ovario (OVCA) foron tratadas con diferentes compostos que modulan a ferroptose para analizar o efecto que teñen na capacidade de proliferación. Así mesmo, as OVCA receptoras foron tratados co medio condicionado obtido das OVCA doadoras tratadas cos diferentes moduladores de ferroptose, para valorar se as células ferroptóticas son capaces de propagar o proceso de forma paracrina. Dos dous indutores empregados, RSL3 foi capaz de diminuír a proliferación das OVCA, mentres que a erastina non alterou a capacidad proliferativa das células. Contrariamente ao esperado, o inhibidor DFO afecta a proliferación das células, concretamente diminnuíndola. Pola contra, a ferrostatina-1 non parece alterar a proliferación das células. Asimesmo, o medio condicionado de OVCA tratadas con RSL3 diminuíu a proliferación en OVCAs. A ferroptose convertiuse nunha ferramenta prometedora para o tratamento do cancro e, concretamente para o manexo do cancro de ovario epitelial mediante o uso de moduladores farmacolóxicos do proceso.