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. 2016 Mar;62(3):302-5.
doi: 10.18097/PBMC20166203302.

[Metformin impact on purine metabolism in breast cancer]

[Article in Russian]
O P Shatova  1 , Eu V Butenko  1 , Eu V Khomutov  1 , D S Kaplun  1 , I Eu Sedakov  1 , I I Zinkovych  1
Affiliations

[Metformin impact on purine metabolism in breast cancer]

[Article in Russian]
O P Shatova et al. Biomed Khim. 2016 Mar.

Abstract
in English, Russian

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.

Masshtabnye épidemiologicheskie i klinicheskie issledovaniia prodemonstrirovali éffektivnost' primeneniia metformina v onkologicheskoĭ praktike. Odnako do sikh por net chetkogo ponimaniia o mekhanizmakh realizatsii protivoopukholevogo éffekta dannogo preparata. Tsel' raboty – izuchit' vliianie metformina na aktivnost' adenozindezaminazy i na adenozinergicheskuiu immunosupressiiu v opukholiakh i ikh mikrookruzhenii. Materialom issledovaniia sluzhili vziatye vo vremia operatsii tkani adenokartsinom molochnykh zhelez patsientok, terapiia kotorykh vkliuchala metformin. Patsientki kontrol'noĭ gruppy ne prinimali dannyĭ preparat. Izuchenie aktivnosti adenozindezaminazy i kontsentratsiĭ substrata (adenozina) i produktov (inozina, gipoksantina) provodili metodom vysokoéffektivnoĭ zhidkostnoĭ khromatografii. Poluchennye dannye svidetel'stvuiut, chto priem metformina sushchestvenno izmeniaet pokazateli katabolizma purinovykh nukleotidov v uzle adenokartsinomy molochnoĭ zhelezy. Odnako, ustanovlennogo nami metformin-indutsirovannogo povysheniia aktivnosti adenozindezaminazy okazyvaetsia nedostatochno dlia snizheniia urovnia adenozina v tkani opukholi. Na fone priema metformina, kontsentratsiia adenozina statisticheski znachimo ne izmeniaetsia, a inozina i gipoksantina znachitel'no uvelichivaiutsia.

Keywords: adenosine; adenosine deaminase; breast cancer; hypoxanthine; inosine; metformin.

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