Orlistat induces ferroptosis-like cell death of lung cancer cells / 医学前沿
Frontiers of Medicine
; (4): 922-932, 2021.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-922502
Biblioteca responsável:
WPRO
ABSTRACT
Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Outras Doenças Respiratórias
/
Neoplasias do Pulmão, Traqueia e Brônquios
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Morte Celular
/
Linhagem Celular Tumoral
/
Orlistate
/
Ferroptose
/
Neoplasias Pulmonares
Limite:
Animais
Idioma:
Inglês
Revista:
Frontiers of Medicine
Ano de publicação:
2021
Tipo de documento:
Artigo