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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.

Project description:BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by symmetric arthritis. Coix Seed Oil (CSO) has been shown to reduce inflammation in collagen induced arthritis (CIA) rats. However, the effect of CSO on synovial angiogenesis in RA is unknown. In this study, we aimed to explore whether CSO could inhibit RA synovial angiogenesis and elucidate the underlying mechanisms.MethodsCIA rat models were established and subjected to different doses of CSO treatments for four weeks in vivo. Arthritis index, paw swelling, and weight were recorded to assess clinical symptoms. Hematoxylin and Eosin staining, Safarnin O fast green staining, Micro-CT, Immunohistochemical, and Immunofluorescence (IF) staining were performed to examined changes in synovial and joint tissues. The serum HIF-1α and VEGF-A levels were evaluated through enzyme-linked immunosorbent assay. Fibroblast-like synoviocytes (FLS) of rats was stimulated with tumor necrosis factor-α (TNF-α) for developing inflammatory model in vitro. Optimal concentrations of CSO and TNF-α for stimulation were measured through Cell Counting Kit-8 test. Wound healing and Transwell migration experiments were employed to determine FLS migratory ability. IF staining was performed to assess HIF-1α nuclear translocation in FLS. Protein levels of SIRT1, HIF-1α, VEGF-A, and CD31 were assessed through Western blot. The isolated aortic rings were induced with recombinant rat VEGF-A 165 (VEGF-A165) to observe the CSO inhibitory impact on angiogenesis ex vivo.ResultsCSO attenuated the progression of arthritis in CIA rats, mitigated histopathological deterioration in synovial and joint tissues, significantly inhibited immature vessels labeled with CD31+/αSMA-, and reduced the micro-vessels in VEGF-A165 induced aortic rings. Moreover, it upregulated SIRT1 protein levels in CIA rats and TNF-α induced FLS, but decreased HIF-1α and VEGF-A protein levels. Furthermore, CSO inhibited the migration ability and HIF-1α nuclear translocation of TNF-α induced FLS. Finally, suppressing SIRT1 levels in TNF-α induced FLS enhanced their migration ability, HIF-1α nuclear translocation, and the protein levels of HIF-1α, VEGF-A, and CD31, whereas the inhibitory effect of CSO on TNF-α induced FLS was severely constrained.ConclusionsThis study indicates that CSO can alleviate synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in CIA rats.

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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