3′,4′-Dihydroxyflavonol Modulates the Cell Cycle in Cancer Cells: Implication as a Potential Combination Drug in Osteosarcoma

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′-dihyd...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-07, Vol.14 (7), p.640
Main Authors: Ferreira de Oliveira, José Miguel P., Almeida, Joana Filipa D., Martins, Maria, Proença, Carina, Oliveira, Helena, Fernandes, Eduarda, Santos, Conceição
Format: Article
Language:English
Subjects:
anthracycline
Apoptosis
Bone cancer
bone sarcoma
Cancer therapies
Cell cycle
cell cycle arrest
Chemotherapy
Cyclin-dependent kinases
Disease
doxorubicin
Drug dosages
drug dose reduction
Drug resistance
flavonoid
Flavonoids
Gene expression
Investigations
Kinases
Metastasis
Tumor necrosis factor-TNF
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Summary: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.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph14070640