Metformin impact on purine metabolism in breast cancer

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.

Metformin as target metabolic drug in oncology

“…Больных СД во всем мире около 347 млн человек, из них 90 % страдают СД 2 типа [10]. Самым назначаемым препаратом для дан-ной группы больных является метформин [11].…”

“…Возможно, это подтверждает выска-занное нами предположение о том, что метформин кос-венно, через лактат, влияет на концентрацию аденозина и функциональную активность лимфоцитов [10]. Кроме этого, установлено, что метаболической основой иммунно-го ответа является стимуляция гликолиза [30,31,42].…”

Bioinformatic validation and machine learning-based exploration of purine metabolism-related gene signatures in the context of immunotherapeutic strategies for nonspecific orbital inflammation

“…In the context of rapidly proliferating tumor cells, the requirement for purines intensifies, leading to an upregulation of the de novo synthesis pathway ( 12 ). This heightened demand for purines in tumor cell replication has positioned purine antimetabolites at the forefront of anticancer therapeutics, marking a seminal advancement in the treatment of malignancies such as acute lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia ( 13 ). This paradigm shift towards leveraging purine antimetabolites in the realm of nonneoplastic diseases underscores their potential in modulating disease progression by inhibiting DNA synthesis and curtailing cell growth.…”

Development and validation of prognostic index based on purine metabolism genes in patients with bladder cancer

“…While the salvage pathway, involving the recycling of degraded purine bases, caters to the majority of cellular purine requirements, rapidly proliferating cells and tumor cells exhibit heightened demands for purines, often met through upregulation of the de novo synthesis pathway. Notably, purines play a pivotal role in tumor cell replication, thus paving the way for the development of purine antimetabolites as the first-generation anticancer drugs, currently employed in the treatment of acute lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia ( 10 ). These purine antimetabolites exert their therapeutic effect by inhibiting DNA synthesis and impeding cellular proliferation.…”