Inhibition of Tumor Glycolysis by Umbelliferone and its Binding to Glycolytic Proteins
Kangbo Peng1,2,3, Yingxiao Wang1,2,3, Xia Lei1,2,3, Yang Wang1,2,3, Yanfang Yang1,2,3, Song-Tao Wu1★★ Corresponding author
- 1Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
- 2Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, China.
- 3Modern Engineering Research Center of Traditional Chinese Medicine and Ethnic Medicine of Hubei Province, Wuhan, China.
CORRESPONDENCE
Song-Tao Wu
Key Laboratory of Traditional Chinese Medicine Resources and Chemistry, Faculty of Pharmacy, Hubei University of Chinese Medicine, Hongshan, Wuhan, Hubei 430065, China.
Received: 21-10-2022; Accepted: 11-11-2022.
Volume 19, Issue 3 · pp. 626–637 · PUBLISHED 2023 · DOI: 10.1177/09731296231170256
View on Pharmacogn. Mag. original site ↗
ABSTRACT
Background and Objectives: Both primary and secondary cancers require the involvement of glycolytic pathways. Cancer cell proliferation leads to the upregulation of glycolysis, which results in increased glucose consumption. For demonstrating that umbelliferone can effectively bind to several proteins involved in the glycolytic pathway, thereby inhibiting glycolysis and reducing cancer cell proliferation. Materials and Methods: This study uses transcriptomics, network pharmacology, and molecular docking to predict the potential targets and possible pathways of umbelliferone against cancer and microscale thermophoresis (MST) to detect the affinity between umbelliferone and potential targets. Results: Transcriptomic analysis revealed that differentially expressed genes were primarily associated with glycolytic and other metabolic pathways and proteins. According to network pharmacology and molecular docking results, glycolysisrelated proteins such as glucose-6-phosphate isomerase (GPI), glycerol-3-phosphate dehydrogenase, mitochondrial (GPD2), phosphoglycerate kinase 2 (PGK2), and heat shock protein HSP-90 alpha (Hsp90AA1) are potential targets of umbelliferone against tumors. MST confirmed that umbelliferous lactone binds strongly to GPI, GPD2, and PGK2 but not to Hsp90AA1. Conclusion: By binding to the glycolysis-related proteins such as GPI, GPD2, and PGK2, umbelliferone acts as an anti-tumor agent by inhibiting glycolysis, cutting off the energy supply to tumor tissue, and reducing tumor growth. It was suggested that umbelliferone might be a brand-new tumor glycolysis inhibitor and that these glycolysis-related proteins might be potential new targets for cancer therapy. This finding helped to establish a solid foundation for the anti-cancer action of umbelliferone.
KEYWORDS
REFERENCES
As publishedShowing references and in-text citations exactly as published.
Cite this article
SELECT FORMAT
Peng, K., Wang, Y., Lei, X., Wang, Y., Yang, Y., & Wu, S. (2023). Inhibition of Tumor Glycolysis by Umbelliferone and its Binding to Glycolytic Proteins. Pharmacognosy Magazine, 19(3), 626–637. https://doi.org/10.1177/09731296231170256