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Coix Seed Oil Exerts an Anti-Triple-Negative Breast Cancer Effect by Disrupting miR-205/S1PR1 Axis.

ABSTRACT: Coix Seed Oil (CSO) possesses a wide range of pharmacological activities. Kanglaite Injection, a commercial product of CSO, has been used clinically as an anticancer drug in China for decades. However, its molecular mechanisms on triple-negative breast cancer (TNBC) remains to be elucidated. In this study, the effect of CSO was evaluated on murine TNBC 4T1 cells and the orthotopic tumor-bearing mouse model and underlying mechanisms were explored. CSO suppressed cell proliferation, colony formation in vitro, and tumor growth in vivo. miR-205-5p was substantially altered in CSO treated tumor tissues compared to the control group by miRNA-sequencing analysis. Sphingomyelin metabolism (SM) decreased in serum in model group compared to the control group, while it increased by CSO administration by lipid metabolomics analysis. The expression of sphingosine 1 phosphate receptor 1 (S1PR1), the critical effector of SM, was downregulated upon CSO treatment. Mechanically, miRNA-205 directly targeted S1PR1 to regulate SM and cell proliferation. CSO reduced the expression of S1PR1, cyclinD1, and phosphorylation levels of STAT3, MAPK, and AKT while upregulated p27. These results revealed that CSO exerted an anti-TNBC effect via the miR-205/S1PR1 axis to regulate sphingomyelin metabolism, and the downstream STAT3/MAPK/AKT signal pathways were partly involved.

SUBMITTER: Fang T

PROVIDER: S-EPMC7556270 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Coix Seed Oil Exerts an Anti-Triple-Negative Breast Cancer Effect by Disrupting miR-205/S1PR1 Axis.

Fang Ting T Jiang Yi-Xin YX Chen Long L Huang Ling L Tian Xin-Hui XH Zhou Yu-Dong YD Nagle Dale G DG Zhang Dan-Dan DD

Frontiers in pharmacology 20200925

Coix Seed Oil (CSO) possesses a wide range of pharmacological activities. Kanglaite Injection, a commercial product of CSO, has been used clinically as an anticancer drug in China for decades. However, its molecular mechanisms on triple-negative breast cancer (TNBC) remains to be elucidated. In this study, the effect of CSO was evaluated on murine TNBC 4T1 cells and the orthotopic tumor-bearing mouse model and underlying mechanisms were explored. CSO suppressed cell proliferation, colony formati ...[more]

PMID: 33101013

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Project description:PurposeA transferrin-modified microemulsion carrying coix seed oil and tripterine (Tf-CT-MEs) was developed for improved tumor-specific accumulation and penetration to enhance cervical cancer treatment.Materials and methodsTripterine-loaded coix seed oil microemulsion (CT-MEs) was prepared through one-step emulsion method. The morphology, size, and zeta potential of CT-MEs and Tf-CT-MEs were examined by transmission electron microscopy and dynamic light scattering. The cellular uptake and mechanisms of HeLa cells were investigated by flow cytometry. Intratumor penetration was investigated using a HeLa three-dimensional (3D) tumor spheroid as the model. The cytotoxicity of the CT-MEs and Tf-CT-MEs against HeLa cells were evaluated by the MTT assay. Additionally, the apoptotic rate of CT-MEs and Tf-CT-MEs inducing apoptosis in HeLa cells was evaluated.ResultsIn the physicochemical characterization, coix seed oil and CT-MEs exhibited a small size (32.47±0.15 nm) and nearly neutral surface charge (-0.36±0.11 mV). After modification with transferrin, the particle size of Tf-CT-MEs slightly increased to 40.02±0.21 nm, but the zeta potential decreased remarkably to -13.63±1.31 mV. The IC50 of Tf-CT-MEs against HeLa cells was 0.7260 µM, which was 2.58-fold lower than that of CT-MEs. In cellular studies, the intracellular fluorescence intensity of fluorescein isothiocyanate (FITC)-labeled Tf-CT-MEs (FITC/Tf-CT-MEs) was 2.28-fold higher than that of FITC-labeled CT-MEs (FITC/CT-MEs). The fluorescence signal of Tf-CT-MEs was observed at 350 µm below the surface of the 3D tumor spheroid. The apoptotic rate of cells treated with Tf-CT-MEs was 1.73- and 2.77-fold higher than that of cells treated with CT-MEs and tripterine, respectively, which was associated with mitochondrial-targeted delivery of tripterine. Moreover, Tf-CT-MEs was capable of significantly downregulating the cellular level of antiapoptotic proteins and arrested cell proliferation in the G2/M phase.ConclusionTaken together, Tf-CT-MEs holds promising potential to be an efficient drug delivery system for combinational therapy of cervical cancer.

Dataset Information

Coix Seed Oil Exerts an Anti-Triple-Negative Breast Cancer Effect by Disrupting miR-205/S1PR1 Axis.

Publications

Coix Seed Oil Exerts an Anti-Triple-Negative Breast Cancer Effect by Disrupting miR-205/S1PR1 Axis.

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