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Published on: November 1, 2017
Liposomal Thiostrepton Formulation and Its Effect on Breast Cancer Growth Inhibition
Sudtirak Wongkhieo1, Katawut Numdee2, Eric W F Lam3
1Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; National Nanotechnology Centre (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand.
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.
Insights
Liposome-encapsulated thiostrepton (TSLP) enhances breast cancer treatment by effectively inhibiting Forkhead box M1 (FOXM1) and inducing cancer cell death. This nanodelivery system improves thiostrepton
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Forkhead box M1 (FOXM1) is a key regulator in breast cancer progression.
- FOXM1 inhibition is a promising strategy for novel cancer therapies.
- Thiostrepton is a potent inhibitor of FOXM1.
Purpose of the Study:
- To develop a liposome-encapsulated thiostrepton (TSLP) nanodelivery system.
- To evaluate the physicochemical properties and biological activities of TSLP.
- To assess TSLP's efficacy in inhibiting breast cancer cells and reducing toxicity.
Main Methods:
- Liposome encapsulation of thiostrepton.
- Characterization using Transmission Electron Microscopy (TEM) and dynamic light scattering.
- Biological evaluation including cellular internalization, MTT assay, spheroid formation assay, and RT-PCR.
Main Results:
- TSLP nanoparticles measured 152 ± 2 nm with a polydispersity index (PdI) of 0.23 ± 0.02 and zeta potential of -20.2 ± 0.1 mV.
- TSLP demonstrated superior reduction of FOXM1 levels in MCF-7 cells compared to free thiostrepton.
- TSLP significantly enhanced the specific inhibition of MCF-7 cell viability and induced cell death in both 2D and 3D cultures, with minimal effect on fibroblast (HDFn) cells.
Conclusions:
- TSLP represents a potential advancement in nanodelivery systems for cancer therapy.
- The TSLP system improves the efficacy and specificity of thiostrepton for breast cancer inhibition.
- TSLP effectively induces cancer cell death while decreasing non-specific toxicity.
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