1. Inicio
  2. Publicaciones
  3. Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice

Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice

Fecha de publicación: Fecha Ahead of Print:

Autores de CIPF

Participantes ajenos a CIPF

  • Lerida-Viso, A
  • Estepa-Fernandez, A
  • Morella-Aucejo, A
  • Lozano-Torres, B
  • Alfonso, M
  • Blandez, JF
  • Bisbal, V
  • Sepulveda, P
  • Garcia-Fernandez, A

Grupos de Investigación

Abstract

Many anticancer agents used in clinics induce premature senescence in healthy tissues generating accelerated aging processes and adverse side-effects in patients. Cardiotoxicity is a well-known limiting factor of anticancer treatment with doxorubicin (DOX), a very effective anthracycline widely used as antitumoral therapy in clinical practice, that leads to long-term morbidity and mortality. DOX exposure severely affects the population of cardiac cells in both mice and human hearts by inducing premature senescence, which may represent the molecular basis of DOX-induced cardiomyopathy. Here, we demonstrate that senescence induction in the heart contributes to impaired cardiac function in mice upon DOX treatment. Concomitant elimination of senescent cells with the senolytic Navitoclax in different formulations produces a significant decrease in senescence and cardiotoxicity markers together with the restoration of the cardiac function in mice followed by echocardiography. These results evidence the potential clinical use of senolytic therapies to alleviate cardiotoxicities induced in chemotherapy-treated patients.

Datos de la publicación

ISSN/ISSNe:
1043-6618, 1096-1186

PHARMACOLOGICAL RESEARCH  Elsevier Inc.

Tipo:
Article
Páginas:
106356-106356
PubMed:
35843569

Citas Recibidas en Web of Science: 53

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • Doxorubicin; Cardiac senescence; Senolytic; Navitoclax; Nanoparticles; Prodrug

Campos de Estudio

Financiación

Generalitat Valenciana (PROMETEO 2018/024)
Generalitat Valenciana (PROMETEO/2019/065)
Instituto de Salud Carlos III (CD19/00038)
Instituto de Salud Carlos III (IFI17/00039)
PAID-10-17
Spanish Government (FPU15/02707)
Spanish Government (FPU17/05454)
Spanish Government (MCUI/FEDER, EU) (RTI2018-100910-B-C41)
Spanish Government (MCUI/FEDER, EU) (RTI2018-101599-B-C22)
Spanish Government (PID2020-115048RB-I00)

Proyectos asociados

Ensuring long-term sustainability of excellence in chemical biology within Europe and beyond

Investigador Principal: MARIA JESUS VICENT DOCON

COMMISSION OF EUROPEAN COMMUNITIES . 2019

MEMBDEATH: Muerte celular y membranas: un nuevo nicho en la lucha contra el cáncer. Colab con la UV, no recibimos financiación

Investigador Principal: MARIA MAR ORZÁEZ CALATAYUD

CONSELLERIA DE EDUCACION . 2019

El interactoma de membrana de las proteínas de la familia Bcl-2 como diana antitumoral

Investigador Principal: MARIA MAR ORZÁEZ CALATAYUD

MINISTERIO DE CIENCIA, INNOVACION Y UNIVERSIDADES . 2021

VALORIZATION OF A FIRST-IN-CLASS MCL-1 INHIBITOR

Investigador Principal: MARIA MAR ORZÁEZ CALATAYUD

MINISTERIO DE CIENCIA, INNOVACION Y UNIVERSIDADES . 2021

Compartir