Related Experiment Video
Updated: Sep 15, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Demethylzeylasteral inhibits proliferation and metastasis of osteosarcoma cells by modulating the PI3K/AKT/Autophagy
Xuhui Yuan1, Jiayu Li1, Bo Yu2
1Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Background:
Osteosarcoma (OS) remains a highly aggressive malignancy with limited treatment options, necessitating the discovery of novel therapeutic agents. Demethylzeylasteral (DEM), a compound previously shown to exert anti-tumor properties in several malignancies, has not been sufficiently explored for its potential in OS treatment.
Purpose:
This study focused on the anti-tumor properties of DEM on OS cells as well as the potential mechanisms.
Methods:
OS cell lines (MG63 and 143B) were exposed to varying concentrations of DEM, followed by assessment of diverse cell functions. RNA sequencing was implemented to identify the molecular pathways affected by DEM exposure. The mechanistic underpinnings of DEM's action were also studied via a series of assays. Additionally, the therapeutic potential was validated utilizing xenograft models.
Results:
DEM evidently repressed OS cell proliferation in a dose- and time-dependent fashion, arrested cells in G2/M phase, and facilitated apoptosis through the modulation of the BCL2/BAX ratio. Furthermore, DEM suppressed cell migration and invasion by reversing EMT-related protein expression. RNA sequencing revealed that DEM primarily affected autophagy-related pathways, particularly through the PI3K/AKT signaling. DEM treatment led to an elevation in ROS generation and enhanced autophagic activity, as demonstrated by elevated LC3B puncta formation and autophagy-related protein expression. In vivo, DEM effectively suppressed tumor growth while showing a favorable safety profile.
Conclusion:
This study provides comprehensive evidence that DEM exerts potent anti-tumor properties in OS via the PI3K/AKT pathway, highlighting the significance of DEM as a therapeutic candidate for OS.
Insights
Demethylzeylasteral (DEM) effectively inhibits osteosarcoma (OS) growth by inducing apoptosis and suppressing migration. This compound shows promise as a novel therapeutic agent for OS by targeting the PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma (OS) is an aggressive cancer with limited treatment options.
- Demethylzeylasteral (DEM) has shown anti-tumor potential in other cancers but its role in OS is unexplored.
Purpose of the Study:
- To investigate the anti-tumor effects of DEM on OS cells.
- To elucidate the underlying molecular mechanisms of DEM's action in OS.
Main Methods:
- OS cell lines (MG63, 143B) were treated with DEM, followed by functional assays and RNA sequencing.
- Mechanisms were explored through various assays, and in vivo efficacy was tested using xenograft models.
Main Results:
- DEM inhibited OS cell proliferation, induced G2/M phase arrest, and promoted apoptosis by altering the BCL2/BAX ratio.
- DEM suppressed cell migration and invasion by reversing epithelial-mesenchymal transition (EMT) markers.
- RNA sequencing identified autophagy and PI3K/AKT signaling as key pathways affected by DEM, leading to increased ROS and autophagic activity.
- In vivo studies confirmed DEM's tumor-suppressive effects and favorable safety profile.
Conclusions:
- DEM exhibits significant anti-osteosarcoma properties through the PI3K/AKT pathway.
- DEM represents a promising therapeutic candidate for osteosarcoma treatment.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:23Abnormal Proliferation
01:20The JAK-STAT Signaling Pathway