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3',4'-Dihydroxyflavonol Modulates the Cell Cycle in Cancer Cells: Implication as a Potential Combination Drug in
José Miguel P Ferreira de Oliveira1, Joana Filipa D Almeida2, Maria Martins2
1LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Abstract:
New agents are demanded to increase the therapeutic options for osteosarcoma (OS). Although OS is the most common bone cancer in children and adolescents, it is considered a rare disorder. Therefore, finding adjuvant drugs has potential to advance therapy for this disease. In this study, 3',4'-dihydroxyflavonol (DiOHF) was investigated to assess the effects in OS cellular models in combination with doxorubicin (Dox). MG-63 and U2OS human OS cells were exposed to DiOHF and Dox and tested for cell viability and growth. To elucidate the inhibitory effects of DiOHF, additional studies were conducted to assess apoptosis and cell cycle distribution, gene expression quantification of cell cycle regulators, and cytokinesis-block cytome assay to determine nuclear division rate. DiOHF decreased OS cell growth and viability in a concentration-dependent manner. Its combination with Dox enabled Dox dose reduction in both cell lines, with synergistic interactions in U2OS cells. Although no significant apoptotic effects were detected at low concentrations, cytostatic effects were demonstrated in both cell lines. Incubation with DiOHF altered cell cycle dynamics and resulted in differential cyclin and cyclin-dependent kinase expression. Overall, this study presents an antiproliferative action of DiOHF in OS combination therapy via modulation of the cell cycle and nuclear division.
Insights
3
Area of Science:
- Oncology
- Pharmacology
Background:
- Osteosarcoma (OS) is a rare bone cancer in children and adolescents, necessitating novel therapeutic strategies.
- Adjuvant drug development is crucial for advancing osteosarcoma treatment options.
Purpose of the Study:
- To investigate the efficacy of 3',4'-dihydroxyflavonol (DiOHF) as an adjuvant therapy for osteosarcoma.
- To evaluate the combined effects of DiOHF and doxorubicin (Dox) in human OS cellular models.
Main Methods:
- Assessed cell viability, growth, apoptosis, and cell cycle distribution in MG-63 and U2OS cells treated with DiOHF and Dox.
- Quantified gene expression of cell cycle regulators and performed cytokinesis-block proliferation assay.
Main Results:
- DiOHF demonstrated a concentration-dependent decrease in OS cell growth and viability.
- Combination therapy with DiOHF allowed for Dox dose reduction and showed synergistic effects in U2OS cells.
- DiOHF exhibited cytostatic effects, altered cell cycle dynamics, and modulated nuclear division.
Conclusions:
- DiOHF exhibits antiproliferative activity in osteosarcoma cells.
- DiOHF shows potential as an adjuvant agent in combination therapy for osteosarcoma by modulating cell cycle and nuclear division.
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