Enhanced Nuclear Translocation and Activation of Aryl Hydrocarbon Receptor (Ahr) in Thp-1 Monocytic Cell Line by a Novel Niosomal Formulation of Indole-3-Carbinol Publisher Pubmed



Abbaspour Sani N¹ ; Hasani M¹ ; Kianmehr A^{1, 2} ; Mohammadi S^{3, 4} ; Sheikh Arabi M⁵ ; Yazdani Y^{4, 6} Show Affiliations
Source: Journal of Liposome Research Published:2020

Abstract

Although niosomes structurally resemble liposomes, they are composed of nonionic surfactants which result in less toxicity and more stability. Here, we developed a novel niosomal formulation of I3C and investigated the nuclear translocation and activation of AhR among human acute myeloid leukaemia (AML) monocytic THP-1 cell line. Niosomal vesicles comprised of nonionic surfactants, cholesterol and I3C were prepared using thin film hydration (TFH) method and characterized according to the entrapment efficiency (EE %), size and zeta potential, by Dynamic light scattering method (DLS), and the surface morphology visualized by Transmission electron microscopy (TEM). In vitro release of I3C was evaluated and MTS assay was used to evaluate the viability of THP-1 cells. The nuclear translocation of AhR was assessed by immunocytochemistry (ICC) and Real-time RT-PCR was conducted using AhR target genes. The ratio of Cholesterol:Span 60 (1:1) niosomal formulations with the highest significant EE% were selected. I3C exerted cytotoxic effects on THP-1 cells in a dose- and time-dependent manner, while administration of niosomal I3C reduced these effects. Both niosomal and free I3C formulations facilitated the nuclear translocation of AhR. CYP1A1 was overexpressed in response to both free and niosomal I3C treatments, while IL1β was overexpressed merely in niosomal I3C-treated THP-1 cells. Niosomal formulation of I3C resulted in reduced cytotoxicity effects by enhancing the functional effects of I3C on AhR in THP-1 cells, including its nuclear translocation and overexpression of the target genes. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.