Abstract 2069: A novel berbamine derivative induces apoptosis of chemotherapy-resistant human osteosarcoma cells through activation of ROS/JNK signaling

Author(s):  
Fan Yang ◽  
Sangkil Nam ◽  
Robin Zhao ◽  
Yan Tian ◽  
David Horne ◽  
...  
Author(s):  
Shubin Wang ◽  
Zongguang Li ◽  
Wei Liu ◽  
Guojun Wei ◽  
Naichun Yu ◽  
...  

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.


2021 ◽  
Vol 134 ◽  
pp. 111155
Author(s):  
Lulu Zhang ◽  
Chunmei Yang ◽  
Yanran Huang ◽  
Huakun Huang ◽  
Xiaohui Yuan ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Yu ◽  
Yuxi Chen ◽  
Shaohui Yuan ◽  
Yang Cao ◽  
Zhenggang Bi

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.


2016 ◽  
Author(s):  
Jose M Moran ◽  
Olga Leal-Hernandez ◽  
Maria L Canal-Macias ◽  
Jesus M Lavado-Garcia ◽  
Raul Roncero-Martin ◽  
...  

2017 ◽  
Vol 17 (3) ◽  
pp. 424-433 ◽  
Author(s):  
Juan Cadavid-Vargas ◽  
Ignacio Leon ◽  
Susana Etcheverry ◽  
Eduardo Santi ◽  
Maria Torre ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Katerina Gioti ◽  
Anastasia Papachristodoulou ◽  
Dimitra Benaki ◽  
Nektarios Aligiannis ◽  
Alexios-Leandros Skaltsounis ◽  
...  

Oleuropein (OLEU) is the most distinguished phenolic compound found in olive fruit and the leaves of Olea europaea L., with several pharmacological properties, including anti-cancer actions. Adriamycin (ADR) is an anthracycline widely used as a chemotherapeutic agent, although it presents significant side effects. The aim of the present study was to investigate the effect of oleuropein alone (20 μg/mL) and in co-treatment with ADR (50 nM), in MG-63 human osteosarcoma cells. Therefore, cellular and molecular techniques, such as MTT assay, flow cytometry, real-time Polymerase Chain Reaction (PCR), western blot and Elisa method, as well as Nuclear Magnetic Resonance (NMR) spectroscopy, were applied to unveil changes in the signal transduction pathways involved in osteosarcoma cells survival. The observed alterations in gene, protein and metabolite levels denote that OLEU not only inhibits MG-63 cells proliferation and potentiates ADR’s cytotoxicity, but also exerts its action, at least in part, through the induction of autophagy.


Sign in / Sign up

Export Citation Format

Share Document