Open Access

Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression

  • Authors:
    • Mengzhe Zhang
    • Fenfen Xiang
    • Yipeng Sun
    • Rongrong Liu
    • Qian Li
    • Qing Gu
    • Xiangdong Kang
    • Rong Wu
  • View Affiliations

  • Published online on: December 18, 2023     https://doi.org/10.3892/or.2023.8686
  • Article Number: 27
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ursolic acid (UA), a natural pentacyclic triterpenoid, is known to exhibit various biological activities and anticancer effects. However, the underlying anticancer mechanism is not fully understood to date. The present study aimed to investigate the antimetastatic effect of UA through ADP‑ribosylation factor like GTPase 4C (ARL4C) in colon cancer. A lung metastasis model of colon cancer in nude mice was established through tail vein injection. A Cell Counting Kit‑8 assay was used to investigate the proliferation of colon cancer cells. Transwell assays were used to detect cell migration and invasion. The expression levels of proteins including ARL4C, matrix metallopeptidase 2 (MMP2), phosphorylated (p)‑AKT and p‑mTOR were measured using western blot analysis. Immunohistochemistry was used to determine the protein expression level in tissues. ARL4C ubiquitination levels were analysed using immunoprecipitation and western blotting. The results indicated that UA inhibits the metastasis of colon cancer in vivo and in vitro. The expression of ARL4C in human colon cancer tissue was significantly higher than that in adjacent tissues and its high expression level was associated with lymph node metastases and tumour stage. UA treatment significantly decreased ARL4C and MMP2 protein levels and inhibited the AKT/mTOR signalling pathway. Overexpression of ARL4C reversed the inhibitory effect of UA on the invasion and migration of HCT‑116 and SW480 cells, as well as the expression and secretion of MMP2 protein. In addition, UA and an AKT signalling pathway inhibitor (LY294002) induced the ubiquitination of the ARL4C protein, which was reversed by a proteasome inhibitor (MG‑132). Collectively, it was revealed in the present study that UA served as a novel solution to relieve colon cancer metastasis by inducing the ubiquitination‑mediated degradation of ARL4C by modulating the AKT signalling pathway. Thus, UA may be a promising treatment option to prolong the survival of patients with colon cancer metastasis.
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February-2024
Volume 51 Issue 2

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Copy and paste a formatted citation
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Spandidos Publications style
Zhang M, Xiang F, Sun Y, Liu R, Li Q, Gu Q, Kang X and Wu R: Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression. Oncol Rep 51: 27, 2024.
APA
Zhang, M., Xiang, F., Sun, Y., Liu, R., Li, Q., Gu, Q. ... Wu, R. (2024). Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression. Oncology Reports, 51, 27. https://doi.org/10.3892/or.2023.8686
MLA
Zhang, M., Xiang, F., Sun, Y., Liu, R., Li, Q., Gu, Q., Kang, X., Wu, R."Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression". Oncology Reports 51.2 (2024): 27.
Chicago
Zhang, M., Xiang, F., Sun, Y., Liu, R., Li, Q., Gu, Q., Kang, X., Wu, R."Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression". Oncology Reports 51, no. 2 (2024): 27. https://doi.org/10.3892/or.2023.8686