1. Academic Validation
  2. Quercetin inhibits glycolysis and tumor progression in a cell line-dependent manner, involving PI3K/AKT signaling predominantly in HOS cells

Quercetin inhibits glycolysis and tumor progression in a cell line-dependent manner, involving PI3K/AKT signaling predominantly in HOS cells

  • Naunyn Schmiedebergs Arch Pharmacol. 2026 Jan 29. doi: 10.1007/s00210-026-05047-9.
Yang Zhou # 1 Liquan Wang # 1 Kang Cheng # 1 2 Jingwen Chen 1 Jiale Lv 1 Chao Song 3 4 Zhijiang Fu 5 Zongchao Liu 6 7 8
Affiliations

Affiliations

  • 1 Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China.
  • 2 Chuzhou Hospital of Integrated Traditional Chinese and Western Medicine, Chuzhou, Anhui Province, China.
  • 3 Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China. [email protected].
  • 4 Department of Orthopedics, RuiKang Hospital affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region,, China. [email protected].
  • 5 Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China. [email protected].
  • 6 Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China. [email protected].
  • 7 Luzhou Longmatan District People's Hospital, Luzhou, Sichuan Province, China. [email protected].
  • 8 , No.182 Chunhui Road, Longmatan District, Luzhou City, Sichuan Province, China. [email protected].
  • # Contributed equally.
Abstract

Osteosarcoma (OS) is a malignant tumor of the bone that primarily affects teenagers. Its extensive replication and metastasis are fuelled by high-energy metabolic expenditure, particularly aerobic glycolysis. The flavonol molecule quercetin has been shown to have beneficial inhibitory effects on Cancer cells. Although the exact mechanism underlying the effective inhibition of OS cell growth and migration differs depending on the type of cell, it plays a significant role in this regard. Using public gene Sequencing data, limma and WGCNA differential analysis, target and pathway enrichment analysis identified key targets of glycolysis in osteosarcoma. In addition, in vitro tests, including the cell viability assay, the ATP and lactate assay, the live/dead cell staining, the crystal violet staining, and the western blot, were used to examine the distinct inhibition of glycolysis by quercetin in the various fractional cell lines of OS. We pinpoint the primary glycolytic targets (PFKM, GYS1, LDHA, SLC2A1, and HK2) that set OS apart from healthy tissue. Quercetin inhibits glycolysis and tumor progression in a cell line-dependent manner, involving PI3K/Akt signaling predominantly in HOS cells. In summary, our work revealed a substantial quantitative difference between the cellular fractions of OS in which quercetin strongly slowed glycolysis.

Keywords

Differentiation; Glucose metabolism; Network pharmacology; Osteosarcoma; Quercetin.

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