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Toward G-Quadruplex-Based Anticancer Agents: Biophysical and Biological Studies of Novel AS1411 Derivativesстатья Исследовательская статья Электронная публикация
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 2 декабря 2020 г.
- Авторы: Ogloblina Anna M., Iaccarino Nunzia, Capasso Domenica, Di Gaetano Sonia, Garzarella Emanuele U., Dolinnaya Nina G., Yakubovskaya Marianna G., Pagano Bruno, Amato Jussara, Randazzo Antonio
- Журнал: International Journal of Molecular Sciences
- Том: 21
- Номер: 20
- Год издания: 2020
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 7781
- DOI: 10.3390/ijms21207781
- Аннотация: Certain G-quadruplex forming guanine-rich oligonucleotides (GROs), including AS1411,are endowed with cancer-selective antiproliferative activity. They are known to bind to nucleolinprotein, resulting in the inhibition of nucleolin-mediated phenomena. However, multiplenucleolin-independent biological effects of GROs have also been reported, allowing them to beconsidered promising candidates for multi-targeted cancer therapy. Herein, with the aim ofoptimizing AS1411 structural features to find GROs with improved anticancer properties, we havestudied a small library of AS1411 derivatives differing in the sequence length and base composition.The AS1411 derivatives were characterized by using circular dichroism and nuclear magneticresonance spectroscopies and then investigated for their enzymatic resistance in serum and nuclearextract, as well as for their ability to bind nucleolin, inhibit topoisomerase I, and affect the viability of MCF-7 human breast adenocarcinoma cells. All derivatives showed higher thermal stabilityand inhibitory effect against topoisomerase I than AS1411. In addition, most of them showed animproved antiproliferative activity on MCF-7 cells compared to AS1411 despite a weaker binding tonucleolin. Our results support the hypothesis that the antiproliferative properties of GROs are due tomulti-targeted effects.
- Добавил в систему: Долинная Нина Германовна