Targeting CDK4/6 in Cancer: Molecular Docking and Cytotoxic Evaluation of <i>Thottea siliquosa</i> Root Extract
<b>Background</b>: Cyclin-dependent kinases 4 and 6 (CDK4/6) are pivotal regulators of the cell cycle, whose dysregulation is closely linked to cancer progression. While synthetic CDK4/6 inhibitors such as Palbociclib and Ribociclib are clinically effective, their use is limited by signi...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1658 |
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| Summary: | <b>Background</b>: Cyclin-dependent kinases 4 and 6 (CDK4/6) are pivotal regulators of the cell cycle, whose dysregulation is closely linked to cancer progression. While synthetic CDK4/6 inhibitors such as Palbociclib and Ribociclib are clinically effective, their use is limited by significant adverse effects. <b>Methods:</b> In this study, the aqueous root extract of <i>Thottea siliquosa</i>, a traditionally used medicinal plant, was evaluated for its potential as a natural CDK4/6 inhibitor. Phytochemical profiling using GC-MS identified bioactive compounds, which were subsequently subjected to molecular docking, ADME prediction, and in vitro cell-based assays using HCT116 and L929 cells. <b>Results:</b> The docking results revealed that Isocorydine (−7.4 kcal/mol for CDK4 and −7.2 kcal/mol for CDK6) and Thunbergol (−6.5 kcal/mol for CDK4 and −7.0 kcal/mol for CDK6) exhibited promising binding affinities comparable to standard CDK inhibitors, Palbociclib (−7.2, −8.3 kcal/mol) and Ribociclib (−7.1, −8.1 kcal/mol). Among the other tested natural compounds, Squalene (−7.1 kcal/mol for CDK4) and 2-palmitoylglycerol (−5.2 kcal/mol for CDK4, −4.9 kcal/mol for CDK6) demonstrated moderate binding affinities. ADME analysis confirmed favorable drug-like properties with minimal toxicity alerts. The extract displayed dose-dependent cytotoxicity with an IC<sub>50</sub> of 140 μg/mL and reduced cell migration in HCT116 cells, indicating potential anti-proliferative effects. These findings suggest that <i>T. siliquosa</i> root extract, through synergistic phytochemical interactions, holds promise as a multi-targeted, plant-based therapeutic candidate for CDK4/6-associated cancers, warranting further in vitro and in vivo validation. |
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| ISSN: | 2227-9059 |