Liposomal Thiostrepton Formulation and Its Effect on Breast Cancer Growth Inhibition

Abstract

Forkhead box M1 (FOXM1) is known to play a role in breast cancer progression. FOXM1 inhibition becomes one of the strategies in developing the novel cancer therapy. Recently, thiostrepton has been recognized as a potent FOXM1 inhibitor. To improve its potential, we aimed to develop a nanodelivery system for thiostrepton. Here, liposome-encapsulated thiostrepton (TSLP) was developed. Physiochemical properties were characterized by TEM and dynamic light scattering technique. The biological activities were also evaluated, by cellular internalization, MTT assay, spheroid formation assay and RT-PCR. The result showed that the range sizes of TSLP were 152 ± 2 nm, polydispersity index (PdI) of 0.23 ± 0.02 and zeta potential of -20.2 ± 0.1 mV. As expected, TSLP showed a higher potential in reducing FOXM1 levels in MCF-7 cells than free thiostrepton. Additionally, TSLP significantly improved the efficiently and specificity of thiostrepton in reducing cell viability of MCF-7, but not of the fibroblast (HDFn) cells. Interestingly, TSLP had an ability to induce MCF-7 cell death in both 2D monolayer and 3D spheroid culture. In conclusions, TSLP could possibly be one of the potential developments using nano-delivery system to improve abilities and specificity of thiostrepton in breast cancer cell inhibition and death inducing, with decreasing non-specific toxicity.

Keywords: Breast cancer; Drug delivery; FOXM1; Growth inhibition; Liposome; Liposome-encapsulated thiostrepton; MCF-7; Nanoparticle; Spheriod; Thiostrepton.