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

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.

Gossypetin Is a Novel Modulator of Inflammatory Cytokine Production and a Suppressor of Osteosarcoma Cell Growth

“…For all conditions, including DMSO solvent control, the DMSO concentration was 0.1% in complete DMEM. The flavonoid concentrations and the incubation period used in the cytotoxicity assays were based on previous studies in OS cell lines incubated with flavonoids of a similar chemical structure [ 42 , 43 ]. For the subsequent assays, the cells were incubated with flavonoids at concentrations below the half-maximal inhibitory concentration (IC 50 ) values determined in the cytotoxicity assays.…”

P12–37 Investigation of the cytotoxicity of bioceramic nanoparticles on Saos-2 cells by an alternative method

“…Nevertheless, as OS therapy is still limited by poor overall survival rates for patients with recurrent OS, novel therapeutic agents are still required. In recent years, several polyphenolic compounds have been described to inhibit several processes related to cancer and to OS in particular [2]. These observations highlight the potential of this type of molecule in OS therapy.The aim of the present study was to evaluate the in vitro cytotoxicity of a group of chlorinated flavonoids in OS.…”