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Pentamidine inhibit S100A4 - p53 interaction and decreases cell proliferation activity
Revansiddha H Katte1, Ruey-Hwang Chou2, Chin Yu1
1Department of Chemistry, National Tsing Hua University, Hsinchu, 30013, Taiwan.
Archives of Biochemistry and Biophysics
|July 11, 2020
Summary
Metastasis-associated S100A4 protein destabilizes tumor suppressor p53. Pentamidine disrupts this interaction, increasing p53 activity and reducing cancer cell proliferation, offering a new therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Metastasis-associated S100A4 protein is overexpressed in various cancers, promoting metastasis.
- S100A4 targets tumor suppressor p53, regulating collagen expression and cell proliferation.
- S100A4 interaction destabilizes wild-type p53.
Purpose of the Study:
- To investigate the interaction between S100A4, p53, and pentamidine.
- To explore the potential of disrupting the S100A4-p53 interaction for cancer therapy.
Main Methods:
- ¹H-¹⁵N HSQC NMR experiments
- HADDOCK modeling
- WST-1 cell proliferation assay using MCF-7 cells
Main Results:
- S100A4 binds to the transactivation domain (TAD) of p53 and pentamidine in the presence of calcium ions.
- Pentamidine shares a similar binding site on S100A4 as p53 TAD, suggesting competitive binding.
- Pentamidine increases p53 activity and reduces cell proliferation in MCF-7 cells.
Conclusions:
- Disrupting the S100A4-p53 interaction can inhibit cancer progression.
- S100A4-p53 inhibitors represent a promising new therapeutic approach for cancer treatment.
Keywords:
High ambiguity driven protein-protein docking (HADDOCK)Nuclear magnetic resonanceS100A4p53 N TAD (1–73)More Related Videos
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