Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

Background/Aims: Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue. Although treatment effectiveness has improved, the OS survival rate has fluctuated in recent years. Andrographolide (AG) has been reported to have antitumor activity against a variety of tumors. Our aim was to investigate the effects and potential mechanisms of AG in human osteosarcoma. Methods: Cell viability and morphological changes were assessed by MTT and live/dead assays. Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase-3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and western blot. Cell migration and invasion were detected by wound healing assay and Transwell® experiments. Results: AG dose-dependently reduced the viability of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of OS, and this effect could be reversed with Beclin-1 siRNA. Conclusion: AG inhibits viability and induces autophagic death in OS cells. AG-induced autophagy inhibits the invasion and metastasis of OS.

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Diallyl Disulfide Induces Apoptosis and Autophagy in Human Osteosarcoma MG-63 Cells through the PI3K/Akt/mTOR Pathway

Molecules ◽

10.3390/molecules24142665 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2665 ◽

Cited By ~ 8

Author(s):

Ziqi Yue ◽

Xin Guan ◽

Rui Chao ◽

Cancan Huang ◽

Dongfang Li ◽

...

Keyword(s):

Annexin V ◽

Mtor Pathway ◽

Diallyl Disulfide ◽

Osteosarcoma Cell ◽

Dependent Manner ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

M Phase ◽

Induced Apoptosis

Diallyl disulfide (DADs), a natural organic compound, is extracted from garlic and scallion and has anti-tumor effects against various tumors. This study investigated the anti-tumor activity of DADs in human osteosarcoma cells and the mechanisms. MG-63 cells were exposed to DADs (0, 20, 40, 60, 80, and 100 μM) for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADs inhibited osteosarcoma cell viability in a dose-and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G2/M phase as the DADs concentration was increased. A Western blot analysis was employed to detect the levels of caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and p62 as well as suppression of the mTOR pathway. High expression of LC3-II protein revealed that DADs induced formation of autophagosome. Furthermore, DADs-induced apoptosis was weakened after adding 3-methyladenine, demonstrating that the DADs treatment resulted in autophagy-mediated death of MG-63 cells. In addition, DADs depressed p-mTOR kinase activity, and the inhibited PI3K/Akt/mTOR pathway increased DADs-induced apoptosis and autophagy. In conclusion, our results reveal that DADs induced G2/M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

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Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis

Pharmaceuticals ◽

10.3390/ph14030260 ◽

2021 ◽

Vol 14 (3) ◽

pp. 260

Author(s):

Yi-Hsien Hsieh ◽

Wen-Hung Hsu ◽

Shun-Fa Yang ◽

Chung-Jung Liu ◽

Ko-Hsiu Lu ◽

...

Keyword(s):

Integrin Αvβ3 ◽

Migration And Invasion ◽

Steroidal Saponin ◽

Αvβ3 Integrin ◽

Osteosarcoma Cells ◽

Inhibitory Effects ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Timosaponin Aiii

Timosaponin AIII (TSAIII) is a steroidal saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal F-actin and cytoskeletal-related proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis. In the synergistic inhibitory analysis, cotreatment of TSAIII with αVβ3 integrin inhibitor [Cyclo(RGDyK)] or focal adhesion kinase (FAK) inhibitor (PF-573228) exerted greater synergistic inhibitory effects on the expression of Intergin αVβ3/FAK/cofilin axis, thus inhibiting the migration and invasion capacities of human osteosarcoma cells. TSAIII was demonstrated to significantly inhibit the pulmonary metastasis formation of human osteosarcoma cells in vivo in metastasis animal models. These findings reveal the inhibitory effects of TSAIII on the metastasis progression of human osteosarcoma cells and the regulation of integrin-αVβ3-FAK-Src and TESK1/p-cofilin mediated cytoskeletal F-actin pathway. Therefore, TSAIII might represent a novel strategy for the auxiliary treatment of human osteosarcoma cells.

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Evodiamine Induces Apoptosis, G2/M Cell Cycle Arrest, and Inhibition of Cell Migration and Invasion in Human Osteosarcoma Cells via Raf/MEK/ERK Signalling Pathway

Medical Science Monitor ◽

10.12659/msm.909682 ◽

2018 ◽

Vol 24 ◽

pp. 5874-5880 ◽

Cited By ~ 6

Author(s):

Yuelai Zhou ◽

Jinlong Hu

Keyword(s):

Cell Cycle ◽

Cell Migration ◽

Cell Cycle Arrest ◽

Migration And Invasion ◽

Osteosarcoma Cells ◽

M Cell ◽

Cell Migration And Invasion ◽

Human Osteosarcoma ◽

Cycle Arrest ◽

Human Osteosarcoma Cells

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Expression of concern: MicroRNA-379 inhibits the proliferation, migration and invasion of human osteosarcoma cells by targeting EIF4G2

Bioscience Reports ◽

10.1042/bsr-20160542_eoc ◽

2020 ◽

Vol 40 (8) ◽

Keyword(s):

Migration And Invasion ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells

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

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500956 ◽

2021 ◽

Vol 49 (08) ◽

pp. 2017-2031

Author(s):

Kyung-Ran Park ◽

Yoon-Ju Kwon ◽

Myounglae Cho ◽

Il Keun Kwon ◽

Jin Tae Hong ◽

...

Keyword(s):

Annexin V ◽

Mg63 Cell ◽

Underlying Mechanism ◽

Mapk Signaling ◽

Migration And Invasion ◽

Boyden Chamber ◽

Antitumor Effects ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Induced Apoptosis

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.

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Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells

Natural Product Communications ◽

10.1177/1934578x1601100418 ◽

2016 ◽

Vol 11 (4) ◽

pp. 1934578X1601100 ◽

Cited By ~ 1

Author(s):

Jose M. Moran ◽

Olga Leal-Hernandez ◽

Maria L. Canal-Macías ◽

Raul Roncero-Martin ◽

Rafael Guerrero-Bonmatty ◽

...

Keyword(s):

Cell Lines ◽

Osteosarcoma Cell ◽

Dependent Manner ◽

Osteosarcoma Cells ◽

Probit Regression ◽

Cytotoxic Effects ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Mg63 Cells ◽

Human Osteosarcoma Cell

In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4–475.0 μM for MG63 cells and from 798.7–359.9 μM for Saos2 cells).

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