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Ursonic acid inhibits migration and invasion of human osteosarcoma cells through the suppression of mitogen-activated protein kinases and matrix metalloproteinases

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Abstract

Introduction

Osteosarcoma (OS) is the most common form of bone malignancy. Although contemporary chemotherapy and surgery have improved the prognosis of those with OS, develo** new OS therapies has proven difficult for some time. The activation of the matrix metalloproteinase (MMP) and mitogen-activated protein kinase (MAPK) signaling pathways can induce metastasis, which is an obstacle to OS treatment. Ursonic acid (UNA) is a phytochemical with the potential to cure a variety of human ailments, including cancer.

Methods and results

In this study, we investigated the anti-tumor properties of UNA in MG63 cells. We conducted colony formation assay, wound healing assay, and Boyden chamber assays to investigate the anti-OS effects of UNA. UNA was found to significantly inhibit the proliferative, migratory, and invasive abilities of MG63 cells. This bioactivity of UNA was mediated by the inhibition of extracellular signal-regulated kinase (ERK) and p38 and reduction of MMP-2 transcriptional expression as observed in western blot analysis, gelatin zymography and RT-PCR. Anti-OS activities of UNA were also observed in Saos2 and U2OS cells, indicating that its anti-cancer properties are not specific to cell types.

Conclusion

Our findings suggest that UNA has the potential for use in anti-metastatic drugs in the treatment of OS.

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Data availability

The datasets generated and analyzed during the study are available from the corresponding author on reasonable request.

Abbreviations

ECM:

Extracellular matrix

ERK:

Extracellular signal-regulated kinase

JNK:

C-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

MDR:

Multidrug resistance

MMP:

Matrix metalloproteinase

NSCLCs:

Non-small-cell lung carcinomas

OS:

Osteosarcoma

PEX:

Hemopexin

RT-PCR:

Real-time polymerase chain reaction

ULA:

Ursolic acid

UNA:

Ursonic acid

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Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT (NRF-2022R1F1A1062695). This research was also supported by Gachon University research fund of 2021 (GCU-202104430001).

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Author notes

  1. Juhyeon Son, Hansol Cha contributed equally to this work.

Authors and Affiliations

  1. Department of Life Sciences, College of BioNano Technology, Gachon University, Seongnam, 13120, Gyeonggi, Korea

    Juhyeon Son, Hansol Cha, Yongwoong Bae & Sang Yeol Lee

  2. Department of Pharmacy and Institute of Pharmaceutical Sciences and Technology, Hanyang University, Ansan, Gyeonggi, Korea

    Sungeun Lee & Chongsuk Ryou

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  1. Juhyeon Son
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  2. Hansol Cha
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Correspondence to Sang Yeol Lee.

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Son, J., Cha, H., Lee, S. et al. Ursonic acid inhibits migration and invasion of human osteosarcoma cells through the suppression of mitogen-activated protein kinases and matrix metalloproteinases. Mol Biol Rep 50, 4029–4038 (2023). https://doi.org/10.1007/s11033-023-08333-4

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