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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| Published in: | Pharmaceuticals (Basel, Switzerland) Vol. 14; no. 7; p. 640 |
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| 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. |
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| AbstractList | 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. |
| Author | Proença, Carina Ferreira de Oliveira, José Miguel P. Martins, Maria Santos, Conceição Fernandes, Eduarda Oliveira, Helena Almeida, Joana Filipa D. |
| AuthorAffiliation | 4 LAQV, REQUIMTE, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal 1 LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; cproenca@ff.up.pt 2 Department of Biology, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal; up201303752@edu.ff.up.pt (J.F.D.A.); up201306375@edu.fc.up.pt (M.M.); csantos@fc.up.pt (C.S.) 3 Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal; holiveira@ua.pt |
| AuthorAffiliation_xml | – name: 1 LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; cproenca@ff.up.pt – name: 3 Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal; holiveira@ua.pt – name: 4 LAQV, REQUIMTE, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal – name: 2 Department of Biology, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal; up201303752@edu.ff.up.pt (J.F.D.A.); up201306375@edu.fc.up.pt (M.M.); csantos@fc.up.pt (C.S.) |
| Author_xml | – sequence: 1 givenname: José Miguel P. orcidid: 0000-0002-3883-0806 surname: Ferreira de Oliveira fullname: Ferreira de Oliveira, José Miguel P. – sequence: 2 givenname: Joana Filipa D. orcidid: 0000-0003-2325-5439 surname: Almeida fullname: Almeida, Joana Filipa D. – sequence: 3 givenname: Maria surname: Martins fullname: Martins, Maria – sequence: 4 givenname: Carina surname: Proença fullname: Proença, Carina – sequence: 5 givenname: Helena surname: Oliveira fullname: Oliveira, Helena – sequence: 6 givenname: Eduarda surname: Fernandes fullname: Fernandes, Eduarda – sequence: 7 givenname: Conceição surname: Santos fullname: Santos, Conceição |
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| SubjectTerms | 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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| Title | 3′,4′-Dihydroxyflavonol Modulates the Cell Cycle in Cancer Cells: Implication as a Potential Combination Drug in Osteosarcoma |
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