11-O-Galloyl Bergenin from Corylopsis coreanas Leaves Induces Autophagy and Apoptosis in Human Osteosarcoma

Abstract

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.

Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells

“…It also activates the PI3K/Akt signaling pathway in vivo and in vitro to reduce Parkinson’s disease symptoms [ 25 ]. Recently, it was shown that bergenin is a novel galectin-3 inhibitor with potential antitumor activity [ 26 ] and inhibits HepG2 cells and decreases the expression of the Bcl-2 family of proteins [ 27 ]. In addition, bergenin increased G1 phase arrest, and reduced expression of Ki67, cycling D1, and cycling B1 in bladder cancer cells [ 28 ].…”