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Updated: May 12, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Demethylzeylasteral inhibits osteosarcoma cell proliferation by regulating METTL17-mediated mitochondrial oxidative
Jingyu Cao1, Haotian Zhang2, Chengbo Wang1
1Institute of Pediatric Medicine, Henan Province Children's Disease Clinical Medical Research Centre, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated of Zhengzhou University, Zhengzhou, China.
Abstract:
Osteosarcoma (OS) represents the most common primary bone malignancy, characterized by substantial disability and mortality, thereby underscoring the critical need for more effective therapeutic interventions to improve clinical outcomes. Demethylzeylasteral (DEM) is a bio-active compound has been reported for its anti-tumor properties through various mechanisms. Nonetheless, the specific effects of DEM on OS have yet to be fully elucidated. This study demonstrated that DEM significantly inhibited OS cell proliferation both in vitro and in vivo. Mechanistically, DEM impairs mitochondrial OXPHOS by targeting METTL17, a known regulator of mitochondrial translation, resulting in reduced ATP production. Subsequent investigations revealed that METTL17 knockdown exerts potent anti-tumor effects in OS, significantly suppressing both in vitro cell proliferation and in vivo xenograft tumor growth. Furthermore, METL17 overexpression significantly alleviated the inhibitory effects of DEM on cell proliferation, while restoring ATP production and oxygen consumption rates. These findings suggest that DEM impedes OS growth by inducing mitochondrial dysfunction through targeting METTL17, thereby highlighting a novel therapeutic strategy and potential molecular target for OS treatment.
Insights
Demethylzeylasteral (DEM) inhibits osteosarcoma (OS) growth by impairing mitochondrial function. Targeting METTL17 with DEM offers a novel therapeutic strategy for this bone cancer.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Osteosarcoma (OS) is a primary bone cancer with high mortality, necessitating novel therapeutic approaches.
- Demethylzeylasteral (DEM), a bioactive compound, exhibits anti-tumor properties, but its role in OS is not fully understood.
Purpose of the Study:
- To investigate the anti-tumor effects of Demethylzeylasteral (DEM) on osteosarcoma (OS).
- To elucidate the underlying molecular mechanisms of DEM's action in OS, focusing on mitochondrial function and METTL17.
Main Methods:
- In vitro and in vivo assays were used to assess the impact of DEM on OS cell proliferation.
- Mitochondrial oxidative phosphorylation (OXPHOS) and ATP production were measured.
- The role of METTL17 was investigated through knockdown and overexpression experiments.
Main Results:
- DEM significantly inhibited OS cell proliferation both in vitro and in vivo.
- DEM impaired mitochondrial OXPHOS by targeting METTL17, leading to reduced ATP production.
- METTL17 knockdown suppressed OS growth, while METTL17 overexpression counteracted DEM's inhibitory effects.
Conclusions:
- Demethylzeylasteral (DEM) exerts anti-osteosarcoma effects by inducing mitochondrial dysfunction via METTL17.
- Targeting METTL17 presents a potential therapeutic strategy for osteosarcoma treatment.
