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Polymeric nanocapsular baicalin: Chemometric optimization, physicochemical characterization and mechanistic anticancer approaches on breast cancer cell lines.

ABSTRACT: Baicalin is a multi-purpose flavonoid known for its anticancer properties, but its application is hindered by its low water solubility and bioavailability. Polymeric nanocapsules were proposed in this work as a promising system for enhancing baicalin delivery, and potentiating its anticancer properties. The characterization of nanocapsules was augmented with chemometric analysis, and the selected formulations were tested on two breast cancer cell lines (MCF-7 and MDA-MB-231), with mechanistic anticancer elucidation using MTT assay, confocal microscopy uptake, flow cytometry, mechanism of cell death, reactive oxygen species production, caspase 3/7 activity and death biomarker expression using quantitative real time PCR. Results showed that baicalin nanocapsules displayed favorable pharmaceutical properties; with the formulation variables affecting their properties elucidated using chemometric factorial analysis. Nanocapsules enhanced the anticancer activity of baicalin up to 216 times for MCF-7 cells and 31 times for MDA-MB-231 after 24?hr incubation. Cellular internalization of the fluorescently labeled nanocapsules was confirmed after 4?hr incubation for both cell lines. Apoptosis was the dominant cell death mechanism, with significant up-regulation of P53 in baicalin nanocapsules treated cells. Data here presented drive to further preclinical studies to investigate the delivery of baicalin polymeric nanocapsules and their anti-cancer activity.

SUBMITTER: I El-Gogary R

PROVIDER: S-EPMC6667692 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Polymeric nanocapsular baicalin: Chemometric optimization, physicochemical characterization and mechanistic anticancer approaches on breast cancer cell lines.

I El-Gogary Riham R Gaber Sara A Abdel SAA Nasr Maha M

Scientific reports 20190730 1

Baicalin is a multi-purpose flavonoid known for its anticancer properties, but its application is hindered by its low water solubility and bioavailability. Polymeric nanocapsules were proposed in this work as a promising system for enhancing baicalin delivery, and potentiating its anticancer properties. The characterization of nanocapsules was augmented with chemometric analysis, and the selected formulations were tested on two breast cancer cell lines (MCF-7 and MDA-MB-231), with mechanistic an ...[more]

PMID: 31363132

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Project description:BackgroundBreast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated.MethodsWe determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer.ResultsThe cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated in common or unique ways.ConclusionsThese two new kinase or "Kin-OMIC" analyses add another dimension of important data about these frequently used breast cancer cell lines. This will assist researchers in selecting the most appropriate cell lines to use for breast cancer studies and provide context for the interpretation of the emerging results.

Dataset Information

Polymeric nanocapsular baicalin: Chemometric optimization, physicochemical characterization and mechanistic anticancer approaches on breast cancer cell lines.

Publications

Polymeric nanocapsular baicalin: Chemometric optimization, physicochemical characterization and mechanistic anticancer approaches on breast cancer cell lines.

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