Тип публикации: статья из журнала
Год издания: 2013
Идентификатор DOI: 10.7868/S023347551305006X
Аннотация: In recent years, new prospects for the use of single-stranded DNA and RNA as therapeutic agents have been discovered. Oligonucleotides that bind to their targets with high affinity and specificity due to the well-defmed tertiary structures and spatial charge distribution are called aptamers. Aptamers can be selected to any molecules, virus particles, bacteria, cells and tissues. They have a wide range of applications from the target identification to drug delivery. Aptamers themselves can affect various cell functions by acting on certain proteins and receptors. Here we present a selection of aptamers with antitumor activity on cancer cell cultures and the identification of their target protein using mass spectrometry analysis. Evolved aptamers showed antitumor properties: aptamer AS-14 (K-d = 3.8 nM) induced apoptosis (translocation phosphatidylserine determined by using Annexin V Alexa Fluor 488) and AS-9 (K-d = 0.75 nM) stopped proliferation (determined by using CellTrace (TM) Far Red DDAO-SE) in the culture of Ehrlich ascites adenocarcinoma cells. Using high performance liquid chromatography and high resolution tandem mass spectrometry, we identified the proteins that were affected by the aptamers. One of the most likely targets for AS-14 was filamin-A, which is involved in the metastasis formation, tumor development, and cell proliferation. According to mass spectrometry data, aptamer AS-9 influences the alpha subunit of mitochondrial ATP synthase, a key component of the mitochondrial oxidative phosphorylation, stimulation of which leads to tumor growth suppression. Thus, mass spectrometry data confirmed the results of the experiments on cells showing that the aptamer binding to specific protein targets causes apoptosis and stops proliferation of cancer cells. However, the mechanisms of aptamer effects in vitro and in vivo are not clear enough and remain to be determined. Our study opens up new possibilities for the creation of non-toxic drugs based on DNA aptamers for targeted anticancer therapy.
Журнал: BIOLOGICHESKIE MEMBRANY
Выпуск журнала: Vol. 30, Is. 5-6
Номера страниц: 398-411
ISSN журнала: 02334755
Место издания: MOSCOW
Издатель: MEZHDUNARODNAYA KNIGA
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