Proteasome inhibitor MG132 induces apoptosis in human osteosarcoma U2OS cells

2021 ◽  
pp. 096032712110179
Author(s):  
Han Ki Lee ◽  
See-Hyoung Park ◽  
Myeong Jin Nam
Keyword(s):  
Signaling Pathways ◽  
Proteasome Inhibitor ◽  
Migration And Invasion ◽  
Apoptotic Signaling ◽  
Antiapoptotic Proteins ◽  
Human Osteosarcoma ◽  
Anticancer Effects ◽  
Caspase 7 ◽  
U2os Cells ◽  
Western Blotting Assay

MG132 is a potent, reversible, and cell-permeable 20S proteasome inhibitor and it is derived from a Chinese medicinal plant. The purpose of this study is to investigate the anticancer effects of MG132 against human osteosarcoma U2OS cells. We first performed MTT and colony formation assays to investigate the anti-proliferative effects of MG132. The results demonstrated that MG132 suppressed the proliferation of U2OS cells. Furthermore, we found that treatment with MG132 increased apoptosis and induced DNA damage in U2OS cells. Additionally, zymography, wound healing, and invasion assays showed that MG132 suppressed the enzymatic activity of matrix metalloproteinases, cell migration, and invasion, respectively of U2OS cells. Furthermore, western blotting assay was performed to investigate the apoptotic signaling pathways in MG132-treated U2OS cells. Our results showed that MG132 downregulated the expression of antiapoptotic proteins, including CDK2, CDK4, Bcl-xL, and Bcl-2, whereas it upregulated the expression of proapoptotic proteins, including p21, p27, p53, p-p53 (ser15, ser20, and ser46), cleaved forms of caspase-3, caspase-7, caspase-9, and PARP, and FOXO3 in U2OS cells. These results demonstrated that MG132 activated apoptotic signaling pathways in U2OS cells. Interestingly, MG132 downregulated the phosphorylation of Akt and Erk. Taken together, our results suggest that MG132 has anticancer effects in U2OS cells. Therefore, MG132 may be a potential therapeutic agent for the treatment of osteosarcoma.

Geraniin inhibits migration and invasion of human osteosarcoma cancer cells through regulation of PI3K/Akt and ERK1/2 signaling pathways

2017 ◽  
Vol 28 (9) ◽  
pp. 959-966 ◽  
Author(s):  
Yanmao Wang ◽  
Daqian Wan ◽  
Runhua Zhou ◽  
Wanrun Zhong ◽  
Shengdi Lu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Signaling Pathways ◽  
Migration And Invasion ◽  
Human Osteosarcoma

Cucurbitacins: A Systematic Review of the Phytochemistry and Anticancer Activity

2015 ◽  
Vol 43 (07) ◽  
pp. 1331-1350 ◽  
Author(s):  
Yuee Cai ◽  
Xiefan Fang ◽  
Chengwei He ◽  
Peng Li ◽  
Fei Xiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mapk Signaling ◽  
Research Progress ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
And Migration

Cucurbitacins are highly oxidized tetracyclic triterpenoids that are widely present in traditional Chinese medicines (Cucurbitaceae family), possess strong anticancer activity, and are divided into 12 classes from A to T with over 200 derivatives. The eight most active cucurbitacin components against cancer are cucurbitacin B, D, E, I, IIa, L glucoside, Q, and R. Their mechanisms of action include antiproliferation, inhibition of migration and invasion, proapoptosis, and cell cycle arrest promotion. Cucurbitacins are also found to be the inhibitors of JAK-STAT3, Wnt, PI3K/Akt, and MAPK signaling pathways, which play important roles in the apoptosis and survival of cancer cells. Recently, new studies have discovered synergistic anticancer effects by using cucurbitacins together with clinically approved chemotherapeutic drugs, such as docetaxel and methotrexate. This paper provides a summary of recent research progress on the anticancer property of cucurbitacins and the various intracellular signaling pathways involved in the regulation of cancer cell proliferation, death, invasion, and migration. Therefore, cucurbitacins are a class of promising anticancer drugs to be used alone or be intergraded in current chemotherapies and radiotherapies to treat many types of cancers.

scholarly journals Indole-3-Carbinol Induces Apoptosis in Human Osteosarcoma MG-63 and U2OS Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Chang Min Lee ◽  
Jongsung Lee ◽  
Myeong Jin Nam ◽  
See-Hyoung Park
Keyword(s):  
Cell Sorting ◽  
Caspase 3 ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dependent Manner ◽  
Facs Analysis ◽  
Caspase 9 ◽  
Human Osteosarcoma ◽  
Caspase 7 ◽  
U2os Cells ◽  
Induced Apoptosis

This study was focused on investigating the anticancer potential of indole-3-carbinol (I3C) against osteosarcoma MG-63 and U2OS cells. A wound healing assay indicated that IC3 inhibited migration of MG-63 and U2OS cells. MTT, WST-1, and colony formation assays revealed that treatment of MG-63 and U2OS cells with I3C decreased cell viability. Fluorescence-activated cell sorting (FACS) analysis showed that I3C induced apoptosis in a dose- and time-dependent manner in MG-63 and U2OS cells. Moreover, via terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP-biotin nick-end labeling (TUNEL) assay, we detected that I3C induced DNA fragmentation. Western blotting demonstrated that activated forms of caspase-3, caspase-7, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP) were increased in MG-63 and U2OS cells, following treatment with I3C. Furthermore, protein expression levels of FOXO3, Bax, and Bim extra-large form were increased while those of Akt, JNK, p38, phosphorylated ERK, and Bcl-xL were decreased by I3C treatment in MG-63 and U2OS cells. Thus, the study indicates that I3C may induce apoptosis in human osteosarcoma MG-63 and U2OS cells via the activation of apoptotic signaling pathways by FOXO3.

scholarly journals Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway

2022 ◽  
Vol 23 (1) ◽  
pp. 484
Author(s):  
Liang-Tsai Yeh ◽  
Chiao-Wen Lin ◽  
Ko-Hsiu Lu ◽  
Yi-Hsien Hsieh ◽  
Chao-Bin Yeh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
U2os Cells

Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential. However, the effect of niclosamide on osteosarcoma cell migration, invasion and the mechanisms underlying have not been fully clarified. Therefore, this study investigated niclosamide’s underlying pathways and antimetastatic effects on osteosarcoma. In this study, U2OS and HOS osteosarcoma cell lines were treated with niclosamide and then subjected to assays for determining cell migration ability. The results indicated that niclosamide, at concentrations of up to 200 nM, inhibited the migration and invasion of human osteosarcoma U2OS and HOS cells and repressed the transforming growth factor beta-induced protein (TGFBI) expression of U2OS cells, without cytotoxicity. After TGFBI knockdown occurred, cellular migration and invasion behaviors of U2OS cells were significantly reduced. Moreover, niclosamide significantly decreased the phosphorylation of ERK1/2 in U2OS cells and the combination treatment of the MEK inhibitor (U0126) and niclosamide resulted in the intensive inhibition of the TGFBI expression and the migratory ability in U2OS cells. Therefore, TGFBI derived from osteosarcoma cells via the ERK pathway contributed to cellular migration and invasion and niclosamide inhibited these processes. These findings indicate that niclosamide may be a powerful preventive agent against the development and metastasis of osteosarcoma.

Reversine induces caspase-dependent apoptosis of human osteosarcoma cells through extrinsic and intrinsic apoptotic signaling pathways

2019 ◽  
Vol 41 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Jae-Sung Kim ◽  
In-A Cho ◽  
Kyeong-Rok Kang ◽  
HyangI Lim ◽  
Tae-Hyeon Kim ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Osteosarcoma Cells ◽  
Apoptotic Signaling ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells
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