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Quercetin induces autophagy-associated death in HL-60 cells through CaMKKβ/AMPK/mTOR signal pathway
- Source :
- Acta Biochimica et Biophysica Sinica, Vol 54, Pp 1244-1256 (2022)
- Publication Year :
- 2022
- Publisher :
- China Science Publishing & Media Ltd., 2022.
-
Abstract
- Acute myeloid leukemia (AML) is one of the most common malignancies of the hematopoietic progenitor cell in adults. Quercetin has gained recognition over the years because of its anti-cancer effect with minimal toxicity. Herein, we aim to investigate the anti-leukemia mechanism of quercetin and to decipher the signaling pathway of quercetin in HL-60 leukemic cells. We observed that quercetin induces apoptosis and autophagic cell death, in which both pathways play an important role in suppressing the viability of leukemia cells. Phosphorylated AMPK (p-AMPK) protein expressions are lower in primary AML cells, HL-60 cells, KG-1 and THP-1 cells than in peripheral blood monocular cells. After quercetin treatment, the expression of p-AMPK is increased while the expression of p-mTOR is decreased in a dose-dependent manner. Mechanistically, compound C, an AMPK phosphorylation inhibitor, upregulates the phosphorylation of mTOR and inhibits autophagy and apoptosis in quercetin-induced HL-60 cells, while silencing of CaMKKβ inhibits the quercetin-induced phosphorylation of AMPK, resulting in increased mTOR phosphorylation. Furthermore, silencing of CaMKKβ inhibits the autophagy in HL-60 cells. Taken together, our data delineate that quercetin plays its anti-leukemia role by inhibiting cell viability and inducing apoptosis and autophagy in leukemia cells. Quercetin inhibits the phosphorylation of mTOR by regulating the activity of AMPK, thus playing a role in the regulation of autophagy and apoptosis. CaMKKβ is a potential upstream molecule for AMPK/mTOR signaling pathway, through which quercetin induces autophagy in HL-60 cells.
Details
- Language :
- English
- ISSN :
- 16729145
- Volume :
- 54
- Database :
- Directory of Open Access Journals
- Journal :
- Acta Biochimica et Biophysica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7c11c894f1e49118174cc222314c94a
- Document Type :
- article
- Full Text :
- https://doi.org/10.3724/abbs.2022117