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Updated: Mar 20, 2026
Colony Formation Assay Detecting the Proliferative Capacity of LncRNA-knockdown Osteosarcoma Cells
Published on: January 16, 2026
MLN4924 suppresses neddylation and induces cell cycle arrest, senescence, and apoptosis in human osteosarcoma
Yi Zhang1,2, Cheng-Cheng Shi2,3, Hua-Peng Zhang4,5
1Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Abstract:
Neddylation is a post-translational protein modification process associated with carcinogenesis and cancer development. MLN4924, a pharmaceutical neddylation inhibitor, induces potent anti-cancer effects in multiple types of cancers. In this study, we investigated the effects of MLN4924 on human osteosarcoma (OS). Levels of both NEDD8 activating enzyme E1 (NAE1) and ubiquitin-conjugating enzyme E2M (Ube2M), two critical components of the neddylation pathway, were much higher in OS tissues and cells than in normal osseous tissues and cells. MLN4924 treatment led to DNA damage, reduced cell viability, senescence and apoptosis in OS cells. Moreover, MLN4924 inhibited OS xenograft tumor growth in mice. Mechanistically, MLN4924 blocked the neddylation of cullins and induced accumulation of several tumor-suppressive substrates of Cullin-RING E3 ubiquitin ligases (CRLs), including CDT1, Wee1, p21, p27, Noxa, and p16. These results suggest clinical studies investigating the utility of MLN4924 for the treatment of OS are warranted.
Insights
MLN4924, a neddylation inhibitor, shows potent anti-cancer effects against human osteosarcoma (OS). This drug induces DNA damage, cell death, and senescence, while inhibiting tumor growth, suggesting its clinical potential for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Neddylation is a post-translational modification linked to cancer development.
- MLN4924 is a pharmaceutical inhibitor of neddylation with demonstrated anti-cancer properties.
- Osteosarcoma (OS) is a primary bone cancer with limited treatment options.
Purpose of the Study:
- To investigate the efficacy of MLN4924 in human osteosarcoma (OS).
- To elucidate the molecular mechanisms underlying MLN4924's effects on OS cells.
Main Methods:
- Assessed neddylation pathway component levels (NAE1, Ube2M) in OS tissues and cells.
- Treated OS cells and xenografts with MLN4924.
- Evaluated DNA damage, cell viability, senescence, apoptosis, and tumor growth.
- Analyzed the neddylation status of cullins and the accumulation of CRL substrates.
Main Results:
- Elevated NAE1 and Ube2M levels were observed in OS tissues and cells.
- MLN4924 induced DNA damage, reduced cell viability, promoted senescence, and triggered apoptosis in OS cells.
- MLN4924 significantly inhibited OS xenograft tumor growth in vivo.
- The drug blocked cullin neddylation and increased levels of tumor suppressors like CDT1, Wee1, p21, p27, Noxa, and p16.
Conclusions:
- MLN4924 demonstrates significant anti-cancer activity against human osteosarcoma.
- The drug's mechanism involves inhibiting neddylation and upregulating tumor-suppressive proteins.
- Clinical trials of MLN4924 for osteosarcoma treatment are warranted.
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