scholarly journals GO-Y078, a Curcumin Analog, Induces Both Apoptotic Pathways in Human Osteosarcoma Cells via Activation of JNK and p38 Signaling

2021 ◽  
Vol 14 (6) ◽  
pp. 497
Author(s):  
Peace Wun-Ang Lu ◽  
Renn-Chia Lin ◽  
Jia-Sin Yang ◽  
Eric Wun-Hao Lu ◽  
Yi-Hsien Hsieh ◽  
...  
Keyword(s):  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Metastatic Potential ◽  
Osteosarcoma Cells ◽  
Curcumin Analog ◽  
Term Survival ◽  
Human Osteosarcoma ◽  
Effector Caspase ◽  
Human Osteosarcoma Cells ◽  
Apoptotic Pathways

Osteosarcoma is the most common primary bone malignancy in teenagers and continues to confer a generally poor prognosis due to its highly metastatic potential. Poor solubility in water and instability of curcumin limits its bioavailability for use in the adjuvant situation to improve the prognosis and the long-term survival of patients with osteosarcoma. To further obtain information regarding the apoptosis induced by a new curcumin analog, GO-Y078, in human osteosarcoma cells, flow cytometric analysis, annexin V-FITC/PI apoptosis staining assay, human apoptosis array, and Western blotting were employed. GO-Y078 dose-dependently decreased viabilities of human osteosarcoma U2OS, MG-63, 143B, and Saos-2 cells and induced sub-G1 fraction arrest and apoptosis in U2OS and 143B cells. In addition to the effector caspase 3 and poly adenosine diphosphate-ribose polymerase, GO-Y078 significantly activated both initiators of extrinsic caspase 8 and intrinsic caspase 9, whereas cellular inhibitors of apoptosis 1 (cIAP-1) and X-chromosome-linked IAP (XIAP) in U2OS and 143B cells were significantly repressed. Moreover, GO-Y078 increased phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2, and p38 in U2OS and 143B cells. Using inhibitors of JNK (JNK-in-8) and p38 (SB203580), GO-Y078′s increases in cleaved caspases 8, 9, and 3 could be expectedly suppressed, but they could not be affected by co-treatment with the ERK inhibitor (U0126). Altogether, GO-Y078 simultaneously induces both apoptotic pathways and cell arrest in U2OS and 143B cells through activating JNK and p38 signaling and repressing IAPs. These findings contribute to a better understanding of the mechanisms responsible for GO-Y078′s apoptotic effects on human osteosarcoma cells.

scholarly journals CLEFMA Activates the Extrinsic and Intrinsic Apoptotic Processes through JNK1/2 and p38 Pathways in Human Osteosarcoma Cells

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3280 ◽  
Author(s):  
Jia-Sin Yang ◽  
Renn-Chia Lin ◽  
Yi-Hsien Hsieh ◽  
Heng-Hsiung Wu ◽  
Geng-Chung Li ◽  
...  
Keyword(s):  
Annexin V ◽  
Synthetic Analog ◽  
Osteosarcoma Cells ◽  
Apoptotic Pathway ◽  
Term Survival ◽  
Anticancer Properties ◽  
Human Osteosarcoma ◽  
Effector Caspase ◽  
Human Osteosarcoma Cells ◽  
Induced Apoptosis

Due to the poor prognosis of metastatic osteosarcoma, chemotherapy is usually employed in the adjuvant situation to improve the prognosis and the chances of long-term survival. 4-[3,5-Bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid (CLEFMA) is a synthetic analog of curcumin and possesses anti-inflammatory and anticancer properties. To further obtain information regarding the apoptotic pathway induced by CLEFMA in osteosarcoma cells, microculture tetrazolium assay, annexin V-FITC/PI apoptosis staining assay, human apoptosis array, and Western blotting were employed. CLEFMA dose-dependently decreased the cell viabilities of human osteosarcoma U2OS and HOS cells and significantly induced apoptosis in human osteosarcoma cells. In addition to the effector caspase 3, CLEFMA significantly activated both extrinsic caspase 8 and intrinsic caspase 9 initiators. Moreover, CLEFMA increased the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2 and p38. Using inhibitors of JNK (JNK-in-8) and p38 (SB203580), CLEFMA’s increases of cleaved caspases 3, 8, and 9 could be expectedly suppressed, but they could not be affected by co-treatment with the ERK inhibitor (U0126). Conclusively, CLEFMA activates both extrinsic and intrinsic apoptotic pathways in human osteosarcoma cells through JNK and p38 signaling. These findings contribute to a better understanding of the mechanisms responsible for CLEFMA’s apoptotic effects on human osteosarcoma cells.

Increased Fas Expression Reduces the Metastatic Potential of Human Osteosarcoma Cells

2004 ◽  
Vol 10 (23) ◽  
pp. 8114-8119 ◽  
Author(s):  
Elizabeth A. Lafleur ◽  
Nadezhda V. Koshkina ◽  
John Stewart ◽  
Shu-Fang Jia ◽  
Laura L. Worth ◽  
...  
Keyword(s):  
Metastatic Potential ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

scholarly journals Licochalcone A-Induced Apoptosis Through the Activation of p38MAPK Pathway Mediated Mitochondrial Pathways of Apoptosis in Human Osteosarcoma Cells In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1441 ◽  
Author(s):  
Lin ◽  
Yang ◽  
Chiou ◽  
Hsieh ◽  
Wen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Osteosarcoma Cells ◽  
Antitumor Effects ◽  
Licochalcone A ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Background: Licochalcone A (LicA) is isolated from the roots of Glycyrrhiza glabra and possesses antitumor and anti-invasive activities against several tumor cells. However, the antitumor effects of LicA on human osteosarcoma cells have yet to be demonstrated either in vitro or in vivo. Methods: Cell viability was measured by MTT assay. Apoptosis and mitochondrial dysfunction were detected with Annexin V/PI staining and JC-1 staining by flow cytometry. The expressions of caspase- or mitochondrial-related proteins were demonstrated by western blotting. Antitumor effect of LicA on 143B xenograft mice in vivo. Results: LicA could inhibit cell proliferation and induce apoptosis in human osteosarcoma cells, as evidenced by a decrease in cell viability, loss of mitochondrial membrane potentials, and activation of caspases. LicA treatment substantially reduced the expression of Bcl-2 and Mcl-1 and increased the expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, and Bax in HOS and U2OS cells. Moreover, mitochondrial membrane potential and apoptosis suppression mediated by Z-VAD or tauroursodeoxycholic acid significantly reduced LicA-induced mitochondria-dependent apoptosis. The study also determined that LicA treatment induced p38MAPK phosphorylation, but siRNA-p38 or BIRB796 substantially reversed cell viability through the inhibition of mitochondria-dependent apoptosis pathways. Finally, an in vivo study revealed that LicA significantly inhibited 143B xenograft tumor growth. Conclusions: These findings demonstrate that LicA has antitumor activities against human osteosarcoma cells through p38MAPK regulation of mitochondria-mediated intrinsic apoptotic pathways in vitro and in vivo.

scholarly journals Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

Molecules ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 75 ◽  
Author(s):  
Muhammad Aziz ◽  
Yazmin Hussin ◽  
Nurul Che Rahim ◽  
Noraini Nordin ◽  
Nurul Mohamad ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Curcumin Analog ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Dependent Signaling Pathway

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

2017 ◽  
Vol 44 (4) ◽  
pp. 1396-1410 ◽  
Author(s):  
Ying Liu ◽  
Yan Zhang ◽  
Jilong Zou ◽  
Lixin Yan ◽  
Xiufeng Yu ◽  
...  
Keyword(s):  
Cell Death ◽  
Morphological Changes ◽  
Annexin V ◽  
Beclin 1 ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

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.

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

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2665 ◽  
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.

Silencing of calpain expression reduces the metastatic potential of human osteosarcoma cells

2009 ◽  
Vol 33 (12) ◽  
pp. 1263-1267 ◽  
Author(s):  
De-Gang Fan ◽  
Jing-Yao Dai ◽  
Juan Tang ◽  
Ming-Mei Wu ◽  
Si-Guo Sun ◽  
...  
Keyword(s):  
Metastatic Potential ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

scholarly journals The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

2018 ◽  
Vol 19 (7) ◽  
pp. 1909 ◽  
Author(s):  
Felipe Lima ◽  
Viviane Seba ◽  
Gabriel Silva ◽  
Guilherme Torrezan ◽  
Carlos Polaquini ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Osteosarcoma Cells ◽  
Curcumin Analog ◽  
Human Osteosarcoma ◽  
Anticancer Effects ◽  
Human Osteosarcoma Cells
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