Synergistic Radiosensitization by Gold Nanoparticles and the Histone Deacetylase Inhibitor SAHA in 2D and 3D Cancer Cell Cultures
| Autor: | Zsolt Rázga, Dávid Kovács, Péter Bélteky, Katalin Hideghéty, Andrea Buhala, Zoltán Kónya, László Tiszlavicz, Zoltán Varga, Nóra Igaz, Krisztina Szőke, Csaba Vizler, Mónika Kiricsi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
DNA damage General Chemical Engineering Article lcsh:Chemistry 03 medical and health sciences 3D cell culture 0302 clinical medicine Radioresistance medicine General Materials Science histone deacetylase inhibitor 030304 developmental biology 0303 health sciences Chemistry Histone deacetylase inhibitor Chromatin lcsh:QD1-999 Cell culture 030220 oncology & carcinogenesis gold nanoparticles Cancer cell Cancer research Radiosensitizing Agent combinational treatment radiosensitization |
| Zdroj: | Nanomaterials Volume 10 Issue 1 Nanomaterials, Vol 10, Iss 1, p 158 (2020) |
| ISSN: | 2079-4991 |
| Popis: | Radiosensitizing agents are capable of augmenting the damage of ionizing radiation preferentially on cancer cells, thereby increasing the potency and the specificity of radiotherapy. Metal-based nanoparticles have recently gathered ground in radio-enhancement applications, owing to their exceptional competence in amplifying the cell-killing effects of irradiation. Our aim was to examine the radiosensitizing performance of gold nanoparticles (AuNPs) and the chromatin-modifying histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alone and in combination. We observed that the colony-forming capability of cancer cells decreased significantly and the DNA damage, detected by &gamma H2AX immunostaining, was substantially greater after combinational treatments than upon individual drug exposures followed by irradiation. Synergistic radiosensitizing effects of AuNPs and SAHA were proven on various cell lines, including radioresistant A549 and DU-145 cancer cells. 3D cultures often manifest radio- and drug-resistance, nevertheless, AuNPs in combination with SAHA could effectively enhance the potency of irradiation as the number of viable cells decreased significantly when spheroids received AuNP + SAHA prior to radiotherapy. Our results imply that a relaxed chromatin structure induced by SAHA renders the DNA of cancerous cells more susceptible to the damaging effects of irradiation-triggered, AuNP-released reactive electrons. This feature of AuNPs should be exploited in multimodal treatment approaches. |
| Databáze: | OpenAIRE |
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