Chrysin-Induced G Protein-Coupled Estrogen Receptor Activation Suppresses Pancreatic Cancer
| Autor: | Hyun Kyung Lim, Hee Jung Kwon, Ga Seul Lee, Jeong Hee Moon, Joohee Jung |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Flavonoids
Proteomics rho-Associated Kinases Organic Chemistry Estrogens General Medicine Catalysis Computer Science Applications Receptors G-Protein-Coupled Inorganic Chemistry Pancreatic Neoplasms Receptors Estrogen GTP-Binding Proteins Cell Line Tumor Humans Physical and Theoretical Chemistry pancreatic cancer chrysin GPER anticancer effect Molecular Biology Spectroscopy Cell Proliferation |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 17; Pages: 9673 |
| ISSN: | 1422-0067 |
| Popis: | Pancreatic cancer (PC) has a high mortality rate due to its poor prognosis and the possibility of surgical resection in patients with the disease. Importantly, adjuvant chemotherapy is necessary to improve PC prognosis. Chrysin, a natural product with anti-inflammatory, antioxidant, and anticancer properties, has been studied for several years. Our previous study demonstrated that chrysin induced G protein-coupled estrogen receptor (GPER) expression and regulated its activity in breast cancer. Herein, we investigated whether chrysin-induced GPER activation suppresses PC progression in MIA PaCa-2 cells and a xenograft model. To determine its mechanism of action, cytotoxicity and clonogenic assays, a FACS analysis, and Western blotting were performed. Furthermore, the delay in tumor growth was evaluated in the MIA PaCa-2-derived xenograft model. Tumor tissues were investigated by Western blotting, immunohistochemistry, and a proteomic analysis. Chrysin caused cell cycle arrest and significantly decreased cell viability. Following co-treatment with chrysin and 17β-estradiol, the inhibitory effect of chrysin on cell proliferation was enhanced. In the xenograft model, chrysin and G1 (a GPER agonist) significantly delayed tumor growth and reduced both Ki-67 (a proliferation marker) and c-Myc expressions in tumor tissues. The proteomic analysis of tumor tissues identified that rho-associated coiled-coil containing protein kinase 1 (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) levels were significantly reduced in chrysin-treated tumor tissues. High ROCK1, TAGLN2, and FCHO2 expressions were indicative of low overall PC survival as found using the Kaplan–Meier plotter. In conclusion, our results suggest that chrysin suppresses PC progression through the activation of GPER and reductions in ROCK1, TAGLN2, and FCHO2 expressions. |
| Databáze: | OpenAIRE |
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