Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells
In this paper, we study the T30923 antiproliferative potential and the contribution of its loop residues in six different human cancer cell lines by preparing five T30923 variants using the single residue replacement approach of loop thymidine with an abasic site mimic (S). G-rich oligonucleotides (...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/5952 |
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| author | Antonella Virgilio Annalisa Pecoraro Daniela Benigno Annapina Russo Giulia Russo Veronica Esposito Aldo Galeone |
| author_facet | Antonella Virgilio Annalisa Pecoraro Daniela Benigno Annapina Russo Giulia Russo Veronica Esposito Aldo Galeone |
| author_sort | Antonella Virgilio |
| collection | DOAJ |
| description | In this paper, we study the T30923 antiproliferative potential and the contribution of its loop residues in six different human cancer cell lines by preparing five T30923 variants using the single residue replacement approach of loop thymidine with an abasic site mimic (S). G-rich oligonucleotides (GRO) show interesting anticancer properties because of their capability to adopt G-quadruplex structures (G4s), such as the G4 HIV-1 integrase inhibitor T30923. Considering the multi-targeted effects of G4-aptamers and the limited number of cancer cell lines tested, particularly for T30923, it should be important to find a suitable tumor line, in addition to considering that the effects also strictly depend on G4s. CD, NMR and non-denaturating polyacrylamide gel electrophoresis data clearly show that all modified ODNs closely resemble the dimeric structure of parallel G4s’ parent aptamer, keeping the resistance in biological environments substantially unchanged, as shown by nuclease stability assay. The antiproliferative effects of T30923 and its variants are tried in vitro by MTT assays, showing interesting cytotoxic activity, depending on time and dose, for all G4s, especially in MDA-MB-231 cells with a reduction in cell viability approximately up to 30%. Among all derivatives, QS12 results are the most promising, showing more pronounced cytotoxic effects both in MDA-MB-231 and Hela cells, with a decrease in cell viability from 70% to 60%. In summary, the single loop residue S substitution approach may be useful for designing antiproliferative G4s, considering that most of them, characterized by single residue loops, may be able to bind different targets in several cancer cell pathways. Generally, this approach could be of benefit by revealing some minimal functional structures, stimulating further studies aimed at the development of novel anticancer drugs. |
| first_indexed | 2024-03-10T01:17:19Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:17:19Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a193ea5f97d543408f105242af4ce4942023-11-23T14:07:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311595210.3390/ijms23115952Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer CellsAntonella Virgilio0Annalisa Pecoraro1Daniela Benigno2Annapina Russo3Giulia Russo4Veronica Esposito5Aldo Galeone6Department of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyIn this paper, we study the T30923 antiproliferative potential and the contribution of its loop residues in six different human cancer cell lines by preparing five T30923 variants using the single residue replacement approach of loop thymidine with an abasic site mimic (S). G-rich oligonucleotides (GRO) show interesting anticancer properties because of their capability to adopt G-quadruplex structures (G4s), such as the G4 HIV-1 integrase inhibitor T30923. Considering the multi-targeted effects of G4-aptamers and the limited number of cancer cell lines tested, particularly for T30923, it should be important to find a suitable tumor line, in addition to considering that the effects also strictly depend on G4s. CD, NMR and non-denaturating polyacrylamide gel electrophoresis data clearly show that all modified ODNs closely resemble the dimeric structure of parallel G4s’ parent aptamer, keeping the resistance in biological environments substantially unchanged, as shown by nuclease stability assay. The antiproliferative effects of T30923 and its variants are tried in vitro by MTT assays, showing interesting cytotoxic activity, depending on time and dose, for all G4s, especially in MDA-MB-231 cells with a reduction in cell viability approximately up to 30%. Among all derivatives, QS12 results are the most promising, showing more pronounced cytotoxic effects both in MDA-MB-231 and Hela cells, with a decrease in cell viability from 70% to 60%. In summary, the single loop residue S substitution approach may be useful for designing antiproliferative G4s, considering that most of them, characterized by single residue loops, may be able to bind different targets in several cancer cell pathways. Generally, this approach could be of benefit by revealing some minimal functional structures, stimulating further studies aimed at the development of novel anticancer drugs.https://www.mdpi.com/1422-0067/23/11/5952guanine-rich oligonucleotidesabasic site mimiccancerantiproliferative G-quadruplex |
| spellingShingle | Antonella Virgilio Annalisa Pecoraro Daniela Benigno Annapina Russo Giulia Russo Veronica Esposito Aldo Galeone Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells International Journal of Molecular Sciences guanine-rich oligonucleotides abasic site mimic cancer antiproliferative G-quadruplex |
| title | Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells |
| title_full | Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells |
| title_fullStr | Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells |
| title_full_unstemmed | Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells |
| title_short | Antiproliferative Effects of the Aptamer d(GGGT)<sub>4</sub> and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells |
| title_sort | antiproliferative effects of the aptamer d gggt sub 4 sub and its analogues with an abasic site mimic loop on different cancer cells |
| topic | guanine-rich oligonucleotides abasic site mimic cancer antiproliferative G-quadruplex |
| url | https://www.mdpi.com/1422-0067/23/11/5952 |
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