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2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells

  • Authors:
    • Hosouk Joung
    • Hyunju Liu
  • View Affiliations / Copyright

    Affiliations: Research Institute of Medical Sciences, Chonnam National University Medical School, Hwasun, Jeonnam 58128, Republic of Korea, Department of Obstetrics and Gynecology, Chosun University College of Medicine, Gwangju 61452, Republic of Korea
    Copyright: © Joung et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 97
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    Published online on: June 14, 2024
       https://doi.org/10.3892/or.2024.8756
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Abstract

2',3',4'‑trihydroxyflavone (2‑D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma (Ut‑LMS) are unknown. The anticancer activity of 2‑D08 was explored in an in vitro model using SK‑LMS‑1 and SK‑UT‑1B cells (human Ut‑LMS cells). Treatment with 2‑D08 inhibited cell viability in a dose‑ and time‑dependent manner and significantly inhibited the colony‑forming ability of Ut‑LMS cells. In SK‑UT‑1B cells treated with 2‑D08, flow cytometric analysis revealed a slight increase in apoptotic rates, while cell cycle progression remained unaffected. Western blotting revealed elevated levels of RIP1, indicating induction of necrosis, but LC3B levels remained unchanged, suggesting no effect on autophagy. A lactate dehydrogenase (LDH) assay confirmed increased LDH release, further supporting the induction of apoptosis and necrosis by 2‑D08 in SK‑UT‑1B cells. 2‑D08‑induced production of reactive oxygen species and apoptosis progression were observed in SK‑LMS‑1 cells. Using Ki67 staining and bromodeoxyuridine assays, it was found that 2‑D08 suppressed proliferation in SK‑LMS‑1 cells, while treatment for 48 h led to cell‑cycle arrest. 2‑D08 upregulated p21 protein expression in SK‑LMS‑1 cells and promoted apoptosis through caspase‑3. Evaluation of α‑SM‑actin, calponin 1 and TAGLN expression indicated that 2‑D08 did not directly initiate smooth muscle phenotypic switching in SK‑LMS‑1 cells. Transcriptome analysis on 2‑D08‑treated SK‑LMS‑1 cells identified significant differences in gene expression and suggested that 2‑D08 modulates cell‑cycle‑ and apoptosis‑related pathways. The analysis identified several differentially expressed genes and significant enrichment for biological processes related to DNA replication and molecular functions associated with the apoptotic process. It was concluded that 2‑D08 exerts antitumor effects in Ut‑LMS cells by modulating multiple signaling pathways and that 2‑D08 may be a promising candidate for the treatment of human Ut‑LMS. The present study expanded and developed knowledge regarding Ut‑LMS management and indicated that 2‑D08 represents a notable finding in the exploration of fresh treatment options for such cancerous tumors.
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Copy and paste a formatted citation
Spandidos Publications style
Joung H and Liu H: 2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells. Oncol Rep 52: 97, 2024.
APA
Joung, H., & Liu, H. (2024). 2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells. Oncology Reports, 52, 97. https://doi.org/10.3892/or.2024.8756
MLA
Joung, H., Liu, H."2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells". Oncology Reports 52.1 (2024): 97.
Chicago
Joung, H., Liu, H."2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells". Oncology Reports 52, no. 1 (2024): 97. https://doi.org/10.3892/or.2024.8756
Copy and paste a formatted citation
x
Spandidos Publications style
Joung H and Liu H: 2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells. Oncol Rep 52: 97, 2024.
APA
Joung, H., & Liu, H. (2024). 2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells. Oncology Reports, 52, 97. https://doi.org/10.3892/or.2024.8756
MLA
Joung, H., Liu, H."2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells". Oncology Reports 52.1 (2024): 97.
Chicago
Joung, H., Liu, H."2‑D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells". Oncology Reports 52, no. 1 (2024): 97. https://doi.org/10.3892/or.2024.8756
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