Related Experiment Video
Updated: Aug 8, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation
Sunny Li-Yun Chang1, Chiang-Wen Lee2, Chen-Yu Yang3
1Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
Abstract:
New therapeutic approaches are needed for metastatic osteosarcoma (OS), as survival rates remain low despite surgery and chemotherapy. Epigenetic changes, such as histone H3 methylation, play key roles in many cancers including OS, although the underlying mechanisms are not clear. In this study, human OS tissue and OS cell lines displayed lower levels of histone H3 lysine trimethylation compared with normal bone tissue and osteoblast cells. Treating OS cells with the histone lysine demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX-1) dose-dependently increased histone H3 methylation and inhibited cellular migratory and invasive capabilities, suppressed matrix metalloproteinase expression, reversed epithelial-to-mesenchymal transition by increasing levels of epithelial markers E-cadherin and ZO-1 and decreasing the expression of mesenchymal markers N-cadherin, vimentin, and TWIST, and also reduced stemness properties. An analysis of cultivated MG63 cisplatin-resistant (MG63-CR) cells revealed lower histone H3 lysine trimethylation levels compared with levels in MG63 cells. Exposing MG63-CR cells to IOX-1 increased histone H3 trimethylation and ATP-binding cassette transporter expression, potentially sensitizing MG63-CR cells to cisplatin. In conclusion, our study suggests that histone H3 lysine trimethylation is associated with metastatic OS and that IOX-1 or other epigenetic modulators present promising strategies to inhibit metastatic OS progression.
Insights
New research shows that low histone H3 trimethylation is linked to metastatic osteosarcoma (OS). The drug IOX-1 boosts this methylation, inhibiting cancer spread and potentially overcoming cisplatin resistance in OS.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Metastatic osteosarcoma (OS) has poor survival rates, necessitating novel therapeutic strategies.
- Epigenetic alterations, specifically histone modifications like histone H3 methylation, are implicated in cancer progression, but their role in OS metastasis is not fully understood.
Purpose of the Study:
- To investigate the association between histone H3 lysine trimethylation and metastatic osteosarcoma.
- To evaluate the therapeutic potential of the histone lysine demethylase inhibitor IOX-1 in inhibiting OS metastasis and overcoming drug resistance.
Main Methods:
- Comparative analysis of histone H3 lysine trimethylation levels in human OS tissues/cells versus normal bone tissues/cells.
- Treatment of OS cells and cisplatin-resistant OS cells with IOX-1.
- Assessment of cellular migration, invasion, epithelial-to-mesenchymal transition (EMT) markers, stemness properties, and ATP-binding cassette transporter expression.
Main Results:
- Lower histone H3 lysine trimethylation was observed in OS tissues and cells compared to normal controls.
- IOX-1 treatment dose-dependently increased histone H3 methylation, inhibited OS cell migration and invasion, suppressed matrix metalloproteinase expression, and reversed EMT.
- IOX-1 also reduced stemness properties in OS cells and increased histone H3 trimethylation and ATP-binding cassette transporter expression in cisplatin-resistant OS cells, suggesting potential chemosensitization.
Conclusions:
- Histone H3 lysine trimethylation is significantly associated with metastatic osteosarcoma.
- IOX-1 demonstrates therapeutic potential by inhibiting OS metastasis and potentially overcoming cisplatin resistance through epigenetic modulation.
More Related Videos
08:47Improved Visualization of Lung Metastases at Single Cell Resolution in Mice by Combined In-situ Perfusion of Lung Tissue and X-Gal Staining of lacZ-Tagged Tumor Cells
Published on: August 21, 2012
08:07Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Related Concept Videos
03:17Inheritance of Chromatin Structures
01:37Epigenetic Regulation
X-chromosome...
01:58X-Inactivation