Ciclopirox olamine sensitizes leukemia cells to natural killer cell-mediated cytolysis by upregulating NKG2DLs via the Akt signaling pathway.
Biochem Biophys Res Commun
; 659: 10-19, 2023 06 04.
Article
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| MEDLINE
| ID: mdl-37030020
ABSTRACT
The activating receptor natural killer group 2D (NKG2D) expressed by Natural killer (NK) cells functions as a "master-switch" in governing the awakening status of NK cells. The NKG2D-mediated cytotoxicity has been declared to be related with the expression levels of NKG2D ligands (NKG2DLs) expressed on tumor cells. Therefore, selective induction of NKG2DLs could be a reliable approach to enhance the efficacy of NK cell-mediated immunotherapy. Our existing study demonstrated that Ciclopirox Olamine (CPX), an off-patent antifungal agent, effectively elevated the expression of NKG2DLs on leukemia cells and sensitized leukemia cells to NK-cell mediated cytolysis. Induction of ROS production and AKT phosphorylation by CPX is essential for the up-regulation of NKG2DLs expressions. Inhibition of AKT by using AKT inhibitor MK2206 decreased both NKG2DLs expressions and NK cell cytotoxicity. These data indicated that increased sensitivity of CPX-treated leukemia cells to NK cell cytolysis was attributed to higher NKG2DLs expressions, resulting from activated AKT signaling pathway. Our findings support the ongoing development of CPX as an anti-tumor agent and suggest its promising immunotherapeutic value in the medication of leukemia.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Leucemia
/
Proteínas Proto-Oncogénicas c-akt
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article