RESUMO
PURPOSE: Fisetin (FIS) is a natural flavonoid with anti-proliferative and anti-apoptotic effects on different human cancer cell lines and can be considered a therapeutic agent for ALL treatment. However, FIS has little aqueous solubility and bioavailability, limiting its therapeutic applications. Thus, novel drug delivery systems are needed to improve solubility and bioavailability of FIS. Plant-derived nanoparticles (PDNPs) could be considered a great delivery system for FIS to the target tissues. In this study, we investigated the anti-proliferative and anti-apoptotic effect of free FIS and FIS-loaded Grape-derived Nanoparticles (GDN) FIS-GDN in MOLT-4 cells. MATERIALS/METHODS: In this study, MOLT-4 cells were treated with increasing concentration of FIS and FIS-GDN and viability of cells were assessed by MTT assay. Additionally, cellular apoptosis rate and related genes expression were evaluated using flow cytometry and Real Time-PCR methods, respectively. RESULTS: FIS and FIS-GDN decreased cells viability and increased cells apoptosis dose-dependently, but not time dependently. Treatment of MOLT-4 cells with increasing concentrations of FIS and FIS-GDN considerably increased the expression of caspase 3, 8 and 9 and Bax level, and also decreased the expression of Bcl-2. Results indicated an increased apoptosis after increased concentration of FIS and FIS-GDN at 24, 48 and 72 h. CONCLUSIONS: Our data proposed that FIS and FIS-GDN can induce apoptosis and have antitumor properties in MOLT-4 cells. Furthermore, compared to FIS, FIS-GDN induced more apoptosis in these cells by increasing the solubility and efficiency of FIS. Additionally, GDNs increased FIS effectiveness in proliferation inhibition and apoptosis induction.
