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Identification of polyoxometalates as inhibitors of basic fibroblast growth factor
Fang Pu1, Enbo Wang, Hongyu Jiang
1State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
Abstract:
Angiogenesis is the process of new blood vessel formation from pre-existing ones. Angiogenic factors contribute to neovascularization that takes place in angiogenesis-dependent diseases, including cancer. Inhibiting the activity of the angiogenic factors to block the angiogenesis pathways is the current strategy of cancer therapy. Basic fibroblast growth factor (bFGF) is regarded as one of the most important angiogenic factors. Herein, we selected polyoxometalates (POMs) with different structures to study the interactions between bFGF and POMs. The results show that POMs could bind to the protein with high affinity, causing detectable changes in conformation and biophysical properties of protein. In addition, POMs could effectively inhibit the cell proliferation induced by bFGF. Significantly, we found that the structure, size and composition of POMs play a key role in the interactions between bFGF and POMs. This study will be meaningful for future screening and design of polyoxometalate-based anticancer drugs.
Insights
Polyoxometalates (POMs) effectively inhibit cancer-promoting basic fibroblast growth factor (bFGF) by binding to it. POM structure influences this interaction, paving the way for new polyoxometalate-based cancer drugs.
Area of Science:
- Biochemistry
- Materials Science
- Oncology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial in diseases like cancer.
- Inhibiting angiogenic factors is a key cancer therapy strategy.
- Basic fibroblast growth factor (bFGF) is a significant angiogenic factor.
Purpose of the Study:
- To investigate the interaction between polyoxometalates (POMs) and bFGF.
- To explore the potential of POMs as anticancer agents by targeting bFGF.
Main Methods:
- Synthesis and selection of POMs with diverse structures.
- Studying the binding affinity and conformational changes of bFGF upon POM interaction.
- Assessing the effect of POMs on bFGF-induced cell proliferation.
Main Results:
- POMs exhibit high-affinity binding to bFGF, altering its conformation and biophysical properties.
- POMs effectively inhibit bFGF-stimulated cell proliferation.
- The structure, size, and composition of POMs critically influence their interaction with bFGF.
Conclusions:
- Polyoxometalates show promise as inhibitors of bFGF.
- POMs' efficacy is dependent on their structural characteristics.
- This research provides a foundation for designing novel polyoxometalate-based anticancer therapeutics.
