The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties
Motivated by the clinical success of gold(I) metallotherapeutic <i>Auranofin</i> in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh<sub>3</sub>)] complex (<b>1</b>), where Hk...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/3/2293 |
| Summary: | Motivated by the clinical success of gold(I) metallotherapeutic <i>Auranofin</i> in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh<sub>3</sub>)] complex (<b>1</b>), where Hkin = kinetin, 6-furfuryladenine, for its in vitro anti-cancer and anti-inflammatory activities. The results revealed that the complex (<b>1</b>) had significant in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, and THP-1), with IC<sub>50</sub> ≈ 1–5 μM, which was even significantly better than that for the conventional platinum-based drug <i>Cisplatin</i> while comparable with <i>Auranofin</i>. Although its ability to inhibit transcription factor NF-κB activity did not exceed the comparative drug <i>Auranofin</i>, it has been found that it is able to positively influence peroxisome-proliferator-activated receptor-gamma (PPARγ), and as a consequence of this to have the impact of moderating/reducing inflammation. The cellular effects of the complex (<b>1</b>) in A2780 cancer cells were also investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential, and shotgun proteomic analysis. Proteomic analysis of R2780 cells treated with complex (<b>1</b>) and starting compounds revealed possible different places of the effect of the studied compounds. Moreover, the time-dependent cellular accumulation of copper was studied by means of the mass spectrometry study with the aim of exploring the possible mechanisms responsible for its biological effects. |
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| ISSN: | 1661-6596 1422-0067 |