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標題: Ursolic Acid Triggers Apoptosis in Human Osteosarcoma Cells via Caspase Activation and the ERK1/2 MAPK Pathway
作者: Wu, Chia-Chieh
Cheng, Chun-Hsiang
Lee, Yi-Hui
Chang, Ing-Lin
Chen, Hsin-Yao
Hsieh, Chen-Pu
Chueh, Pin-Ju
關鍵字: MAPK;MG-63 cells;apoptosis;caspase;ursolic acid;Apoptosis;Bone Neoplasms;Caspase 3;Caspase 8;Caspase 9;Cell Line, Tumor;Humans;MAP Kinase Signaling System;Mitogen-Activated Protein Kinases;Osteosarcoma;Triterpenes
Project: Journal of agricultural and food chemistry, Volume 64, Issue 21, Page(s) 4220-6.
Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, has been shown to trigger apoptosis in several lines of tumor cells in vitro. We found that treatment with UA suppressed the viability of human osteosarcoma MG-63 cells and induced cell cycle arrest at sub-G1 and G2/M phases. Furthermore, exposure to UA induced intracellular oxidative stress and collapse of mitochondrial membrane permeability, resulting in the subsequent activation of apoptotic caspases 8, 9, and 3 as well as PARP cleavage, and ultimately apoptosis in MG-63 cells. Moreover, protein analysis of mitogen-activated protein kinase (MAPK)-related protein expression showed an increase in activated ERK1/2, JNK, and p38 MAPK in UA-treated MG-63 cells. In addition, UA-induced apoptosis was significantly abolished in MG-63 cells that had been pretreated with inhibitors of caspase 3, 8, and 9 and ERK1/2. Furthermore, UA-treated MG-63 cells also exhibited an enhancement in Bax/Bcl-2 ratio, whereas anti-apoptotic XIAP and survivin were down-regulated. Taken together, we provide evidence demonstrating that UA mediates caspase-dependent and ERK1/2 MAPK-associated apoptosis in osteosarcoma MG-63 cells.
DOI: 10.1021/acs.jafc.6b00542
Appears in Collections:生物醫學研究所

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