Effect of Ferroptosis Inducers and Inhibitors on Cell Proliferation in Acute Leukemia.
Anticancer Res
; 44(3): 1003-1010, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38423654
ABSTRACT
BACKGROUND/AIM:
Ferroptosis refers to an iron-dependent mechanism of regulated cell death that is attributable to lipid peroxidation. Ferroptosis has been documented as a therapeutic target for various solid cancers; nonetheless, its implication in leukemia remains ambiguous. Therefore, this study aimed at investigating the impact of ferroptosis inducers and inhibitors on in vitro leukemia cell line proliferation. MATERIALS ANDMETHODS:
Six leukemia cell lines, including acute myeloid leukemia (AML)-derived MV4-11, THP-1, HL-60, and U-937, and T-lymphoblastic leukemia (T-ALL)-derived Jurkat and KOPT-K1 with activating NOTCH1 mutations, were assessed. Erastin, which interrupts cystine uptake and depletes intracellular glutathione, and RAS-selective lethal 3 (RSL3), which suppresses glutathione peroxidase 4 (GPX4), were employed as ferroptosis inducers. Lipid peroxidation-arresting ferrostatin-1 and deferoxamine were used as ferroptosis inhibitors. Cells were cultured with these compounds and cell proliferation was assessed using a colorimetric assay. Additionally, signaling protein expression was monitored using immunoblotting, and the outcome of GPX4 knockdown was evaluated.RESULTS:
Ferroptosis inducers suppressed proliferation in all cell lines except THP-1 for Erastin and THP-1 and Jurkat for RSL3. Although the ferroptosis inhibitors did not affect cell proliferation, they rescued inducer-mediated growth suppression. Ferroptosis inducers impeded MYC and cyclin D3 expression in certain cell lines and NOTCH1 signaling in T-ALL cells. GPX4 knockdown and RSL3 treatment interrupted MYC and cyclin D3 expression, respectively, in four cell lines.CONCLUSION:
Ferroptosis inducers may serve as potential candidates for novel molecular therapy against AML and T-ALL.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Leucemia-Linfoma Linfoblástico de Células T Precursoras
/
Ferroptosis
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón