Vitamin B6 Fuels Acute Myeloid Leukemia Growth

doi:10.1016/j.trecan.2020.03.005

Trends in Cancer

Volume 6, Issue 7, July 2020, Pages 536-537

https://doi.org/10.1016/j.trecan.2020.03.005 Get rights and content

Mounting evidence indicates that vitamins C and D are linked to tumor growth, but the relevance of vitamin B6 remains uncertain. In a recent study, Chen et al. demonstrate that pyridoxal kinase promotes vitamin B6 phosphorylation, producing the active form pyridoxal 5′-phosphate, which regulates two key metabolic enzymes required for acute myeloid leukemia (AML) cell growth.

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No potential conflicts of interest are disclosed.

Acknowledgments

The author apologizes to the researchers whose work was not cited because of space limitation. S.J. is supported by FWCC Legacy Funds (149741373A), Intramural Research Council Support (110251225A), and by the Micro Seed Funds.

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There are more references available in the full text version of this article.

Cited by (2)

Discovery and characterization of natural product luteolin as an effective inhibitor of human pyridoxal kinase
2024, Bioorganic Chemistry
Pyridoxal kinase (PDXK) is an essential enzyme in the synthesis of pyridoxal 5-phosphate (PLP), the active form of vitamin B6, which plays a pivotal role in maintaining the enzyme activity necessary for cell metabolism. Thus, PDXK has garnered attention as a potential target for metabolism regulation and tumor therapy. Despite this interest, existing PDXK inhibitors have faced limitations, including weak suppressive activity, unclear mechanisms of action, and associated toxic side effects. In this study, we present the discovery of a novel PDXK inhibitor, luteolin, through a high-throughput screening approach based on enzyme activity. Luteolin, a natural product, exhibits micromolar-level affinity for PDXK and effectively inhibits the enzyme's activity in vitro. Our crystal structures reveal that luteolin occupies the ATP binding pocket through hydrophobic interactions and a weak hydrogen bonding pattern, displaying reversible characteristics as confirmed by biochemical assays. Moreover, luteolin disrupts vitamin B6 metabolism by targeting PDXK, thereby inhibiting the proliferation of leukemia cells. This research introduces a novel screening method for identifying high-affinity and potent PDXK inhibitors and sheds light on clarification of the structural mechanism of PDXK-luteolin for subsequent structure optimization of inhibitors.
From descriptive to functional genomics of leukemias focusing on genome engineering techniques
2021, International Journal of Molecular Sciences

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Trends in Cancer

SpotlightVitamin B6 Fuels Acute Myeloid Leukemia Growth

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Disclaimer Statement

Acknowledgments

Clin. Lymphoma Myeloma Leuk.

Cancer Cell

Biochim. Biophys. Acta

Cell

Biochem. Biophys. Res. Commun.

Spotlight
Vitamin B6 Fuels Acute Myeloid Leukemia Growth