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      Development of a New Nanocarrier for Dietary Garcinol: Characterization and In Vitro Efficacy Evaluation Using Breast Cancer Stem Cells Grown in Hypoxia

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          Abstract

          Garcinol (GA), a polyisoprenylated benzophenone derivative, is one of the major phytochemicals found in a number of fruits of Garcinia. This study aimed to develop a new nanodelivery system comprising GA, hyaluronic acid (HA), and poly(lactic-co-glycolic acid) (PLGA) to actively target breast cancer stem cells (bCSCs) grown under hypoxic conditions. HA has been reported to show higher affinity for the cluster-determinant 44 receptor (CD44), while PLGA is an FDA-approved biodegradable polymer used in clinical applications. Nanoparticles (NPs) were prepared by emulsion solvent diffusion technique using DMAB as the emulsifier. Following preparation, particle size, surface charge, and polydispersity index of NPs were characterized. Antiproliferative effects of NPs were assessed by the WST-1 cell proliferation assay. Apoptotic effects of NPs were evaluated by the caspase-3/7 assay. Effects of prepared NPs on the expression of genes related to hypoxia-inducing factors (HIF-1α and HIF-2α) and notch ligands (DLL1 and Jagged1) were evaluated using real-time PCR. HA-coated garcinol-loaded NPs (HA-GA-NPs) showed greater antiproliferative effects in bCSCs grown under hypoxia. Moreover, HA-GA-NPs showed an improved cellular uptake via receptor-mediated endocytosis compared to non-HA-coated GA-NPs. Exposure to GA-HA-NPs resulted in a significant downregulation in hypoxia-inducing factors and notch pathway-related genes. Activation of caspase-3/7 confirmed the HA-GA-NPs can induce apoptosis in bCSCs. Overall findings of the study confirm that HA-GA-NPs can be considered as an effective nanodelivery system to target bCSCs grown under the hypoxic microenvironment.

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          Garcinol inhibits esophageal cancer metastasis by suppressing the p300 and TGF-β1 signaling pathways

          J. Ahmad (2010)
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            Author and article information

            Contributors
            (View ORCID Profile)
            Journal
            Journal of Food Quality
            Journal of Food Quality
            Hindawi Limited
            1745-4557
            0146-9428
            February 10 2021
            February 10 2021
            : 2021
            : 1-10
            Affiliations
            [1 ]Institute of Biochemistry, Molecular Biology and Biotechnology, Cumaratunga Munidasa Mawatha, University of Colombo, Colombo 03, Sri Lanka
            [2 ]Department of Chemistry, Faculty of Science, University of Peradeniya, Kandy, Sri Lanka
            Article
            10.1155/2021/6654211
            8c027f60-c97e-46cc-b36f-47e8cfae11c1
            © 2021

            https://creativecommons.org/licenses/by/4.0/

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