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[Metformin impact on purine metabolism in breast cancer]
O P Shatova1, Eu V Butenko1, Eu V Khomutov1
1Gorky Donetsk National Medical University, Donetsk, Ukraine.
Abstract:
Large-scale epidemiological and clinical studies have demonstrated the efficacy of metformin in oncology practice. However, the mechanisms of implementation of the anti-tumor effect of this drug there is still need understanding. In this study we have investigated the effect of metformin on the activity of adenosine deaminase and respectively adenosinergic immunosuppression in tumors and their microenvironment. The material of the study was taken during surgery of breast cacer patients receiveing metformin, and also patients which did not take this drug. The adenosine deaminase activity and substrate (adenosine) and products (inosine, hypoxanthine) concentrations were determined by HPLC. Results of this study suggest that metformin significantly alters catabolism of purine nucleotides in the node breast adenocarcinoma tisue. However, the metformin-induced increase in the adenosine deaminase activity is not sufficient to reduce the level of adenosine in cancer tissue. Thus, in metformin treated patients the adenosine concentration remained unchanged, and inosine and hypoxanthine concentration significantly increased.
Insights
Metformin alters purine metabolism in breast cancer, increasing adenosine deaminase activity. However, this change does not reduce tumor adenosine levels, suggesting complex effects on adenosinergic immunosuppression.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Metformin is widely used in oncology, but its anti-tumor mechanisms require further elucidation.
- Understanding metformin's impact on the tumor microenvironment is crucial for optimizing cancer therapy.
Purpose of the Study:
- To investigate metformin's effect on adenosine deaminase activity and adenosinergic immunosuppression in breast cancer.
- To analyze purine metabolite changes in breast adenocarcinoma tissue related to metformin use.
Main Methods:
- Analysis of breast cancer tissue from patients receiving metformin versus those not on the drug.
- High-Performance Liquid Chromatography (HPLC) was used to quantify adenosine, inosine, hypoxanthine, and adenosine deaminase activity.
Main Results:
- Metformin significantly alters purine nucleotide catabolism in breast adenocarcinoma tissue.
- Increased adenosine deaminase activity due to metformin was insufficient to lower adenosine levels in cancer tissue.
- Patients on metformin showed unchanged adenosine concentrations but significantly increased inosine and hypoxanthine levels.
Conclusions:
- Metformin impacts purine metabolism in breast cancer, affecting adenosine deaminase activity and its products.
- The observed changes suggest a complex interplay between metformin, purine metabolism, and the tumor microenvironment's immunosuppressive potential.
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