11-O-Galloyl Bergenin from Corylopsis coreanas Leaves Induces Autophagy and Apoptosis in Human Osteosarcoma.
Autor: | Park, Kyung-Ran, Kwon, Yoon-Ju, Cho, Myounglae, Kwon, Il Keun, Hong, Jin Tae, Yun, Hyung-Mun |
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Předmět: |
DNA analysis
PROTEINS MEDICINAL plants CELL culture CELL migration OSTEOSARCOMA HETEROCYCLIC compounds AUTOPHAGY CANCER invasiveness ONCOGENES WESTERN immunoblotting IMMUNOHISTOCHEMISTRY MICROBIOLOGICAL assay ANTINEOPLASTIC agents APOPTOSIS NUCLEAR magnetic resonance spectroscopy CELL motility JANUS kinases CELLULAR signal transduction T-test (Statistics) TRADITIONAL medicine LEAVES CELL proliferation RESEARCH funding TRANSFERASES DESCRIPTIVE statistics DOSE-effect relationship in pharmacology PLANT extracts CELL lines MITOGEN-activated protein kinases GENETIC techniques CALCIUM-binding proteins CYTOLOGY DATA analysis software MOLECULAR structure CASPASES PHOSPHORYLATION SPECTROPHOTOMETRY PHARMACODYNAMICS |
Zdroj: | American Journal of Chinese Medicine; 2021, Vol. 49 Issue 8, p2017-2031, 15p |
Abstrakt: | Osteosarcoma is the most common malignant bone-forming tumor, wherein most patients with high grade osteosarcomas are treated with chemotherapy. Despite this, survival for metastatic or relapsed osteosarcoma patients has remained at an overall 5-year survival rate of 20%. In particular, the extracts of Corylopsis coreana (Korean winter hazel), a cultivated woody plant in South Korea, have shown beneficial anti-inflammatory, anti-oxidative, anti-osteoclastic, and antihyperuricemic properties. Therefore, this study aimed to demonstrate the antitumor activities and underlying mechanism of 11-O-Galloyl bergenin (OGAL) isolated from Corylopsis coreanas leaves in human osteosarcoma cells. Herein, we found that OGAL inhibited MG63 cell proliferation and induced cellular apoptosis as evidenced by cleaved-PARP, cleaved-caspase 3, TUNEL-positive cells, and Annexin V-positive cells. Specifically, OGAL-induced apoptosis was accompanied by p53 and p21 upregulation, BAX expression, and decreased Bcl-2 and cdk2. Moreover, OGAL induced autophagy via AKT inactivation, LC3II upregulation, and MG63 cell autophagosome formation. OGAL-induced autophagy was also accompanied by increased p38 phosphorylation, whereas JNK and ERK1/2 activities were found to be unaffected upon examining the MAPK signaling pathway. Furthermore, wound healing and Boyden chamber assays showed that OGAL suppressed MG63 cell migration and invasion. Given these findings, this study provided evidence that OGAL has antitumor effects by apoptosis and autophagy enhancement through increased p53, AKT, and p38 signaling, suggesting that OGAL may be a potential therapeutic strategy for osteosarcoma treatment. [ABSTRACT FROM AUTHOR] |
Databáze: | Complementary Index |
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