Targeting aerobic glycolysis by quercetin inhibits acute monocytic leukemia SHI-1 cells

槲皮素通过靶向有氧糖酵解抑制急性单核细胞白血病SHI-1细胞

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Abstract

BACKGROUND: Quercetin (Que) exhibits antitumor properties. This study aims to investigate whether Que inhibits the proliferation of acute monocytic leukemia SHI-1 cells by suppressing glycolysis and regulating energy metabolism. METHODS: SHI-1 cells were treated with Que. Cell viability, colony-forming ability, and contents of pyruvate, lactate, and ATP of SHI-1 cells were measured. Immunofluorescence staining analyzed the expression of myelocytomatosis oncogene (c-Myc), glucose transporter 1 (GLUT1), PKM2, and p-AMP-activated protein kinase (AMPK). Western blotting and RT-qPCR detected the levels of c-Myc, GLUT1, hexokinase (HK2), PKM2, lactate dehydrogenase, pyruvate dehydrogenase kinase 2, AMPK, mammalian target of rapamycin (mTOR), and p-mTOR in SHI-1 cells. An acute monocytic leukemia model was established in BALB/c nude male mice and administered Que by gavage. RESULTS: Que-suppressed proliferation and reduced pyruvate, lactate, and ATP production in SHI-1 cells. The inhibitory effects of Que on cell viability were reversed by pyruvate. Que-inhibited glycolysis-related proteins and mRNAs in SHI-1 cells. It also declined phosphorylation of AMPK and mTOR. In vivo+, Que slowed SHI-1 xenograft growth and decreased expression of c-Myc, GLUT1, and HK2. CONCLUSION: This study demonstrates that Que exerts antileukemia effects by inhibiting proliferation, glycolysis, and energy metabolism in acute monocytic leukemia cells.

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