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Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway

Shengdong Yang¹, Jin Chen², Tao Tan¹

¹Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.

Cancer Management and Research

|May 20, 2020

Abstract

Background:

Osteosarcoma is the most common primary malignant bone neoplasm and is associated with abysmal prognosis. There are limitations of current treatment methods. Therefore, developing new agents to treat osteosarcoma is exceptionally urgent.

Aim:

This study aimed to evaluate the anticancer effects of evodiamine (EVO) on osteosarcoma cells and, meanwhile, to investigate the underlying mechanisms involved.

Materials And Methods:

The effect of EVO on the proliferation of osteosarcoma was detected by MTT assay, crystal violet assay and colony formation assay. The effects of EVO on the migration and invasion of osteosarcoma were detected by wound-healing assay and transwell assay. The effect of EVO on apoptosis of osteosarcoma was measured by Hoechst 33258 staining and cell cycle assay. The protein expression levels were detected by Western blotting assay. The activity of Wnt/β-Catenin signaling pathway was detected by luciferase reporter assay and Western blotting assay.

Results:

According to MTT, crystal violet and colony formation assay results, EVO significantly inhibited the cell proliferation in a dose-dependent manner. Hoechst 33258 staining assay revealed that EVO induced cell apoptosis in a concentration-dependent manner. Moreover, EVO inhibited the migration and invasion of the osteosarcoma cells. Mechanistic studies revealed that EVO suppresses metastatic through suppressing epithelial-mesenchymal transition (EMT) as indicated by elevating the expression of epithelial marker E-cadherin and reducing the expression of mesenchymal markers N-cadherin and vimentin, as well as EMT transcription factors Snail and MMPs. Subsequently, EVO induced cell cycle arrest at the G2/M phase that correlated with reduced levels of cyclin D1 protein, while the apoptotic effects of EVO were associated with the upregulation of Bax and Bad and a decrease in Bcl-2 protein levels. Furthermore, EVO exerted the anticancer effects by suppressing Wnt/β-catenin signal pathway in osteosarcoma cells.

Conclusion:

In summary, EVO exhibited potent anticancer effects against human osteosarcoma cells and promoted apoptosis through suppressing Wnt/β-catenin signaling pathway. These results indicated that EVO may be regarded as a new approach for osteosarcoma treatment.

Insights

Evodiamine (EVO) demonstrates significant anticancer effects against osteosarcoma cells by inhibiting proliferation, migration, and invasion. EVO promotes apoptosis and cell cycle arrest, offering a potential new treatment strategy for this bone cancer.

Area of Science:

Oncology
Pharmacology
Molecular Biology

Background:

Osteosarcoma is the most common primary bone cancer with a poor prognosis.
Current treatments for osteosarcoma have limitations, necessitating novel therapeutic agents.
Developing new treatments for osteosarcoma is a critical unmet medical need.

Purpose of the Study:

To evaluate the anticancer potential of evodiamine (EVO) in osteosarcoma cells.
To elucidate the underlying molecular mechanisms of EVO's anti-osteosarcoma activity.
To investigate EVO's effects on cell proliferation, apoptosis, migration, and invasion.

Main Methods:

Cell proliferation was assessed using MTT, crystal violet, and colony formation assays.
Cell migration and invasion were evaluated via wound-healing and Transwell assays.
Apoptosis, cell cycle, protein expression (Western blotting), and Wnt/β-catenin pathway activity were analyzed.

Main Results:

EVO significantly inhibited osteosarcoma cell proliferation, migration, and invasion in a dose-dependent manner.
EVO induced apoptosis and G2/M cell cycle arrest, modulating key proteins like Bax, Bad, Bcl-2, and cyclin D1.
EVO suppressed epithelial-mesenchymal transition (EMT) and downregulated the Wnt/β-catenin signaling pathway.

Conclusions:

Evodiamine exhibits potent anticancer effects against human osteosarcoma cells.
EVO promotes apoptosis and inhibits cell cycle progression by suppressing the Wnt/β-catenin pathway.
EVO represents a promising novel therapeutic candidate for osteosarcoma treatment.

Read full analysis

Keywords:

Wnt/β-catenin anticancer evodiamine osteosarcoma

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