scholarly journals Peiminine Induces G0/G1-Phase Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells in Vitro and in Vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Yu ◽  
Yuxi Chen ◽  
Shaohui Yuan ◽  
Yang Cao ◽  
Zhenggang Bi
Keyword(s):  
Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Jnk Signaling ◽  
Human Osteosarcoma ◽  
Phase Arrest ◽  
Human Osteosarcoma Cells ◽  
G1 Phase Arrest ◽  
Jnk Signaling Pathway

Aims: Peiminine has been reported to have various pharmacological properties, including anticancer activity. In this study, we investigated the effect of this alkaloid on osteosarcoma and explored the underlying mechanisms.Methods: To evaluate the antiosteosarcoma effects of peiminine in vitro, cell viability was assessed by CCK-8 and live/dead assays; the effects of the drug on apoptosis and the cell cycle were examined by flow cytometry; the effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively, while its effects on autophagy were observed by transmission electron microscopy and an LC3 fluorescent puncta formation assay. The role of autophagy in the peiminine-mediated effects in osteosarcoma cells was evaluated by CCK-8 assay and western blotting after the application of the autophagy inhibitor chloroquine. The effect of peiminine on reactive oxygen species (ROS) production was analyzed using fluorescence confocal microscopy and spectrophotometry. Additionally, peiminine-treated osteosarcoma cells were exposed to SP600125, a JNK inhibitor, and N-acetylcysteine, a ROS scavenger, after which the contribution of the ROS/JNK signaling pathway to osteosarcoma was assessed using cell viability and LC3 fluorescent puncta formation assays, flow cytometry, and western blotting. A xenograft mouse model of osteosarcoma was generated to determine the antitumor effects of peiminine in vivo.Results: Peiminine suppressed proliferation and metastasis and induced cell cycle arrest, apoptosis, and autophagy in osteosarcoma cells. These anticancer effects of peiminine were found to be dependent on intracellular ROS generation and activation of the JNK pathway. In line with these results, peiminine significantly inhibited xenograft tumor growth in vivo.Conclusions: Peiminine induced G0/G1-phase arrest, apoptosis, and autophagy in human osteosarcoma cells via the ROS/JNK signaling pathway both in vitro and in vivo. Our study may provide an experimental basis for the evaluation of peiminine as an alternative drug for the treatment of osteosarcoma.

scholarly journals Imperatorin induces autophagy and G0/G1 phase arrest via PTEN-PI3K-AKT-mTOR/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Minchao Lv ◽  
Qingxin Xu ◽  
Bei Zhang ◽  
Zhiqiang Yang ◽  
Jun Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bioinformatic Analysis ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Human Osteosarcoma Cells ◽  
G1 Phase Arrest

Abstract Background Osteosarcoma is the third most common cancer in adolescence and the first common primary malignant tumor of bone. The long-term prognosis of osteosarcoma still remains unsatisfactory in the past decades. Therefore, development of novel therapeutic agents which are effective to osteosarcoma and are safe to normal tissue simultaneously is quite essential and urgent. Methods Firstly, MTT assay, cell colony formation assay, cell migration and invasion assays were conducted to evaluate the inhibitory effects of imperatorin towards human osteosarcoma cells. RNA-sequence assay and bioinformatic analysis were then performed to filtrate and assume the potential imperatorin-induced cell death route and signaling pathway. Moreover, quantitative real-time PCR assay, western blot assay and rescue experiments were conducted to confirm the assumptions of bioinformatic analysis. Finally, a subcutaneous tumor-transplanted nude mouse model was established and applied to evaluate the internal effect of imperatorin on osteosarcoma by HE and immunohistochemistry staining. Results Imperatorin triggered time-dependent and dose-dependent inhibition of tumor growth mainly by inducing autophagy promotion and G0/G1 phase arrest in vitro and in vivo. Besides, imperatorin treatment elevated the expression level of PTEN and p21, down-regulated the phosphorylation of AKT and mTOR. In contrast, the inhibition of PTEN using Bpv (HOpic), a potential and selective inhibitor of PTEN, concurrently rescued imperatorin-induced autophagy promotion, cell cycle arrest and inactivation of PTEN-PI3K-AKT-mTOR/p21 pathway. Conclusions This work firstly revealed that imperatorin induced autophagy and cell cycle arrest through PTEN-PI3K-AKT-mTOR/p21 signaling pathway by targeting and up-regulating PTEN in human osteosarcoma cells. Hence, imperatorin is a desirable candidate for clinical treatments of osteosarcoma.

Lycorine Induces Apoptosis and G1 Phase Arrest Through ROS/p38 MAPK Signaling Pathway in Human Osteosarcoma Cells In Vitro and In Vivo

Spine ◽  
2020 ◽  
Vol 45 (3) ◽  
pp. E126-E139 ◽  
Author(s):  
Lei Ning ◽  
Shuanglin Wan ◽  
Zhiwei Jie ◽  
Ziang Xie ◽  
Xiang Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
G1 Phase ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Phase Arrest ◽  
Human Osteosarcoma Cells ◽  
G1 Phase Arrest

Neohesperidin Induces Cell Cycle Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells

2021 ◽  
pp. 1-24
Author(s):  
Shubin Wang ◽  
Zongguang Li ◽  
Wei Liu ◽  
Guojun Wei ◽  
Naichun Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Jnk Signaling ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

Neohesperidin has anti-oxidative and anti-inflammatory properties and exerts extensive therapeutic effects on various cancers. In this study, the osteosarcoma cell lines were exposed to different concentrations of neohesperidin. Cell proliferation and viability were assessed by CCK-8 and colony-formation assays. The role of neohesperidin in cell cycle progression and apoptosis were analyzed by flow cytometry and western blotting. To identify autophagosomes and autolysosomes, we used a tandem GFP-mRFP-LC3B lentiviral construct. In addition, autophagy was evaluated by examining autophagosome formation using transmission electron microscopy. Intracellular reactive oxygen species (ROS) production was detected by fluorescence microscopy and flow cytometry. Subsequently, the activation of the ROS/JNK signaling pathway was investigated. Neohesperidin could inhibit proliferation and induce apoptosis in SJSA and HOS cells. The formation of autophagosomes indicated that autophagy occurred in neohesperidin-treated cells and the apoptotic effect of neohesperidin was significantly increased after the use of autophagy inhibitors. Subsequently, we found that neohesperidin-induced apoptosis and autophagy were related to the increase in ROS generation and were significantly inhibited by GSH. Moreover, neohesperidin induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of JNK with SP600125 attenuated neohesperidin-induced apoptosis and autophagy simultaneously. Our data indicated that neohesperidin caused G2/M phase arrest and induced apoptosis and autophagy by activating the ROS/JNK pathway in human osteosarcoma cells, suggesting that neohesperidin is a potential drug candidate for the treatment of osteosarcomas.

VS-5584 Inhibits Human Osteosarcoma Cells Growth by Induction of G1- phase Arrest through Regulating PI3K/mTOR and MAPK Pathways

2020 ◽  
Vol 20 (8) ◽  
pp. 616-623 ◽  
Author(s):  
Jing-Yi Sun ◽  
Ya-Jun Hou ◽  
Hai-Juan Cui ◽  
Cheng Zhang ◽  
Ming-Feng Yang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
Tube Formation ◽  
G1 Phase ◽  
Mtor Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Phase Arrest ◽  
Human Osteosarcoma Cells ◽  
G1 Phase Arrest

Background: Activation of PI3K/mTOR signaling pathway plays key role in the progression of human osteosarcoma. Studies have confirmed that VS-5584 was a novel inhibitor of PI3K/mTOR pathway, and displayed potential anticancer activity. Objective: To explore the anticancer effect and underlying mechanism of VS-5584 against the growth of human osteosarcoma cells. Methods: U2OS and MG-63 human osteosarcoma cells were cultured and the cytotoxicity, cell apoptosis in VS-5584-treated cells were explored by the CCK8 assay, flow cytometric analysis and western blot. Cell migration and tube formation were also employed to examine the anticancer potential. Results: The results showed that VS-5584 treatment dose-dependently inhibited the growth of U2OS and MG-63 cells by induction of G1-phase arrest through regulating p21, p27, Cyclin B1 and Cdc2. Further investigation revealed that VS-5584 treatment effectively inhibited the PI3K/mTOR signaling pathway and triggered MAPK phosphorylation. Moreover, VS-5584 treatment dramatically suppressed cell migration and tube formation of HUVECs, followed by the down-regulation of HIF-1α and VEGF. Conclusion: Our findings validated that VS-5584 may be a promising anticancer agent with potential application in the chemotherapy and chemoprevention of human osteosarcoma.

scholarly journals Cardamonin inhibits the growth of human osteosarcoma cells through activating P38 and JNK signaling pathway

2021 ◽  
Vol 134 ◽  
pp. 111155
Author(s):  
Lulu Zhang ◽  
Chunmei Yang ◽  
Yanran Huang ◽  
Huakun Huang ◽  
Xiaohui Yuan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Jnk Signaling ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Jnk Signaling Pathway

Guavinoside B from Psidium guajava alleviates acetaminophen-induced liver injury via regulating the Nrf2 and JNK signaling pathways

2020 ◽  
Vol 11 (9) ◽  
pp. 8297-8308
Author(s):  
Yuanyuan Li ◽  
Jialin Xu ◽  
Dongli Li ◽  
Hang Ma ◽  
Yu Mu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Phenolic Compound ◽  
Psidium Guajava ◽  
Jnk Signaling ◽  
Nrf2 Signaling Pathway ◽  
Jnk Signaling Pathway

GUB, a main phenolic compound present in guava fruits, could alleviate APAP-induced liver injury in vitro and in vivo by activating the Nrf2 signaling pathway and inhibiting the JNK signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document