Upregulation of G Protein-Coupled Estrogen Receptor by Chrysin-Nanoparticles Inhibits Tumor Proliferation and Metastasis in Triple Negative Breast Cancer Xenograft Model

Abstract

Triple-negative breast cancer (TNBC) is associated with a high mortality rate among women globally. TNBC shows a high rate of recurrence and distant metastasis. Particularly, the chemotherapy is limited because hormone therapy of breast cancer is ineffective. Thus, an effective chemotherapeutic agent is needed for tumor suppression. Chrysin-nanoparticles (chrysin-NPs) were investigated for their inhibitory effect on a MDA-MB-231-derived xenograft model. To gain insight into the underlying mechanisms, we conducted human matrix metalloproteinase (MMP) array, western blot, and immunohistochemistry analysis. Furthermore, in vivo imaging was used to monitor the chemotherapeutic efficacy of chrysin-NPs in a metastasis mouse model. Chrysin-NPs significantly inhibited the proliferation of MDA-MB-231 cells via the PI3K/JNK pathway and induced cell death through the p53-apoptosis pathway, leading to delayed MDA-MB-231-derived tumor growth. Interestingly, chrysin-NPs significantly induced G protein-coupled estrogen receptor (GPER) expression, which suppresses MMPs and NF-κB expression. Chrysin-NPs acted as effective metastasis inhibitors. Our results suggest that chrysin-NPs may be used as an effective adjuvant formulation to inhibit TNBC progression.

Korean Red Ginseng Enhances Immunotherapeutic Effects of NK Cells via Eosinophils in Metastatic Liver Cancer Model

“…MMP2 and MMP9 are predictors of liver cancer recurrence [ 13 ] and are highly expressed in invasive hepatocellular cancer (HCC) cells [ 14 ]. Inhibition of MMP2 and MMP9 produces anti-metastatic effects in breast cancer [ 15 ] and HCC [ 16 ]. In our study, MMP2 and MMP9 expression levels were decreased by treatment with KRG and the combination of KRG and NK cells.…”

Sex-dependent liver cancer xenograft models for predicting clinical data in the evaluation of anticancer drugs

“…Frozen tumor tissue sections were washed in PBS, incubated in 0.3% H 2 O 2 solution for 10 min, and rinsed in PBS. They were blocked with 5% albumin (GenDEPOT) for 1 h and incubated with anti-Ki-67 antibody (1:100; ab16667, Abcam, Cambridge, UK) overnight at 4 °C as previously described [ 26 ]. The rinsed tissue slides were incubated with the secondary antibody for 1 h at room temperature.…”

“…Tumor tissues were homogenized in a radioimmunoprecipitation assay (RIPA) buffer (GenDEPOT) containing a protease and phosphatase inhibitor cocktail (GenDEPOT) as previously described [ 26 ]. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and transferred on to polyvinylidene fluoride membranes (0.45 μm pore size; Millipore, Darmstadt, Germany).…”

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

“…Chrysin-loaded nanostructures are capable of enhancing apoptosis via triggering p53 expression. Furthermore, chrysin-loaded nanoparticles suppress PI3K/JNK axis and inhibit tumor growth in vivo [ 127 ]. Chrysin enhances miRNA-let-7a expression, while it reduces H19 and COPB2 expression levels to impair progression of gastric cancer cells [ 128 ].…”