The effect of fiestin loaded in grape-derived nanoparticles on acute lymphoblastic leukemia cell line (MOLT-4)

Abstract

Acute lymphoblastic leukemia (ALL) is one of the most common childhood leukemia, which despite many developments in different treatments is still one of the leading causes of death in children due to treatment resistance and recurrence of the disease. Therefore, there is a need for novel and alternative treatments. Fisetin (FIS) is a natural flavonoid which has been exhibited anti-proliferative, anti-inflammatory, anti-apoptotic and antioxidant effects in many human cancer cell lines and can be used in the treatment of ALL. But FIS has little aqueous solubility; bioavailability and low systemic circulation and due to that, the therapeutic applications of it have been prevented. Thus nanotechnology approaches and novel drug delivery systems are needed to improved solubility and bioavailability of FIS. Plant-derived nanoparticles (PDNPs) have several benefits like low toxicity and immunogenicity therefore they could be great therapeutic systems for delivery of FIS to target tissues. However, the effects of FIS on proliferation and apoptosis of human MOLT-4 acute lymphoblastic leukemia cells have rarely been described and the underlying mechanism of intrinsic apoptosis is still unclear. Thus, in this study, we investigated the anti-proliferative and anti-apoptotic effect of free FIS and FIS-loaded plant nanoparticles (FIS-GDN) on MOLT-4 cells. Materials and methods: In this study, MOLT-4 cells treated with increasing concentration of FIS and FIS-GDN and viability of cells were assessed by MTT assay. Also the rate of cellular apoptosis and expression of genes were evaluated using flow cytometry and Real Time-PCR methods. Results: We observed that FIS and FIS-GDN decreased cells viability and increased cells apoptosis after treatment in dose-dependent manner but not time dependent. Data of PCR demonstrated that FIS and FIS-FGN enhanced expression of caspase 3, 8 and 9 and Bax and decreased Bcl-2. Apoptosis induced by FIS and FIS-GDN were decreased over time at 48 and 72 h after treatment compared to 24 h and this result probably due to reduce the effect of the FIS. Thus data indicated that nanoparticles make FIS more effective in inhibiting proliferation and inducing apoptosis.