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SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells

  • Authors:
    • Yuxin Chen
    • Danya Zhang
    • Jie Li
    • Yue Sun
    • Jing Wang
    • Ling Xi
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 202
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    Published online on: February 27, 2025
       https://doi.org/10.3892/ol.2025.14948
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Abstract

SNS‑032 is a synthetic compound that specifically inhibits cyclin‑dependent kinases 2, 7 and 9. Its primary anticancer activity involves cell cycle arrest, which prevents tumor cell growth. However, there are limited reports on whether SNS‑032 induces pyroptosis, a novel inflammation‑mediated programmed cell death pathway in breast cancer (BC). The present study demonstrated that SNS‑032 treatment decreased cell viability by inducing pyroptosis in BC cells. Typical morphological indications of pyroptosis were observed, including cell swelling and destruction of cell membrane integrity, leading the release of adenosine 5'‑triphosphate and lactate dehydrogenase. Furthermore, the expression of caspase‑3, the N terminus of gasdermin E (GSDME) and B‑cell lymphoma‑2 (BCL‑2)‑associated X protein increased, whereas expression of BCL‑2 decreased. In addition, Z‑DEVD‑FMK, a specific caspase‑3 inhibitor, markedly alleviated pyroptosis triggered by SNS‑032. These findings suggested that SNS‑032 induced caspase‑3/GSDME‑dependent pyroptosis. Furthermore, the present study demonstrated that decitabine (DAC), a DNA methyltransferase inhibitor, upregulated the expression of GSDME protein and enhanced SNS‑032‑induced caspase‑3/GSDME‑dependent pyroptosis in BC cells. In conclusion, these results suggest that caspase‑3/GSDME‑induced pyroptosis can be facilitated by SNS‑032 treatment in BC cells, and DAC has the potential to enhance SNS‑032‑induced pyroptosis by increasing GSDME expression. This mechanistic insight indicates that SNS‑032 is a promising therapeutic agent for BC treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Chen Y, Zhang D, Li J, Sun Y, Wang J and Xi L: SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells. Oncol Lett 29: 202, 2025.
APA
Chen, Y., Zhang, D., Li, J., Sun, Y., Wang, J., & Xi, L. (2025). SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells. Oncology Letters, 29, 202. https://doi.org/10.3892/ol.2025.14948
MLA
Chen, Y., Zhang, D., Li, J., Sun, Y., Wang, J., Xi, L."SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells". Oncology Letters 29.4 (2025): 202.
Chicago
Chen, Y., Zhang, D., Li, J., Sun, Y., Wang, J., Xi, L."SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells". Oncology Letters 29, no. 4 (2025): 202. https://doi.org/10.3892/ol.2025.14948
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Y, Zhang D, Li J, Sun Y, Wang J and Xi L: SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells. Oncol Lett 29: 202, 2025.
APA
Chen, Y., Zhang, D., Li, J., Sun, Y., Wang, J., & Xi, L. (2025). SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells. Oncology Letters, 29, 202. https://doi.org/10.3892/ol.2025.14948
MLA
Chen, Y., Zhang, D., Li, J., Sun, Y., Wang, J., Xi, L."SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells". Oncology Letters 29.4 (2025): 202.
Chicago
Chen, Y., Zhang, D., Li, J., Sun, Y., Wang, J., Xi, L."SNS‑032 combined with decitabine induces caspase‑3/gasdermin E‑dependent pyroptosis in breast cancer cells". Oncology Letters 29, no. 4 (2025): 202. https://doi.org/10.3892/ol.2025.14948
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