Open Access

Heparanase inhibitor OGT 2115 induces prostate cancer cell apoptosis via the downregulation of MCL‑1

  • Authors:
    • Xin Li
    • Shuai-Jun Xu
    • Bin Jin
    • Hong-Sheng Lu
    • Shan-Kun Zhao
    • Xiao-Fei Ding
    • Ling-Long Xu
    • Hai-Jun Li
    • Shuang-Chun Liu
    • Jie Chen
    • Guang Chen
  • View Affiliations

  • Published online on: January 5, 2024     https://doi.org/10.3892/ol.2024.14217
  • Article Number: 83
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Heparanase (HPSE), an endo‑β‑D‑glucuronidase, cleaves heparan sulfate and serves an important role in the tumor microenvironment and thus in tumorigenesis. HPSE is known to promote tumor cell evasion of apoptosis. However, the underlying mechanism of this requires further study. In the present study, the results demonstrated that myeloid cell leukemia‑1 (MCL‑1), an antiapoptotic protein, and HPSE were upregulated in prostate cancer tissues compared with adjacent normal tissues. In addition, the HPSE inhibitor, OGT 2115, inhibited PC‑3 and DU‑145 prostate cancer cell viability in a dose‑dependent manner, with IC50 values of 20.2 and 97.2 µM, respectively. Furthermore, annexin V/PI double‑staining assays demonstrated that OGT 2115 induced apoptosis in prostate cancer cells. OGT 2115 treatment markedly decreased MCL‑1 protein expression levels, whereas RNA interference‑mediated downregulation of MCL‑1 and OGT 2115 drug treatment synergistically induced apoptosis in PC‑3 and DU‑145 cells. In vivo, OGT 2115 40 mg/kg (ig) significantly inhibited PC‑3 cell xenograft growth in nude mice and increased the positive TUNEL staining rate of xenograft tissues. It was therefore hypothesized that MCL‑1 was an important signaling molecule in OGT 2115‑induced apoptosis. The results of the present study also demonstrated that the proteasome inhibitor, MG‑132, markedly inhibited the downregulation of MCL‑1 protein expression levels induced by OGT 2115. However, the protein synthesis inhibitor, cycloheximide, did not affect the role of OGT 2115 in regulating MCL‑1. In summary, the results of the present study demonstrated that the proapoptotic activity of OGT 2115 was achieved by downregulating MCL‑1.
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February-2024
Volume 27 Issue 2

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Online ISSN:1792-1082

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Spandidos Publications style
Li X, Xu S, Jin B, Lu H, Zhao S, Ding X, Xu L, Li H, Liu S, Chen J, Chen J, et al: Heparanase inhibitor OGT 2115 induces prostate cancer cell apoptosis via the downregulation of MCL‑1. Oncol Lett 27: 83, 2024.
APA
Li, X., Xu, S., Jin, B., Lu, H., Zhao, S., Ding, X. ... Chen, G. (2024). Heparanase inhibitor OGT 2115 induces prostate cancer cell apoptosis via the downregulation of MCL‑1. Oncology Letters, 27, 83. https://doi.org/10.3892/ol.2024.14217
MLA
Li, X., Xu, S., Jin, B., Lu, H., Zhao, S., Ding, X., Xu, L., Li, H., Liu, S., Chen, J., Chen, G."Heparanase inhibitor OGT 2115 induces prostate cancer cell apoptosis via the downregulation of MCL‑1". Oncology Letters 27.2 (2024): 83.
Chicago
Li, X., Xu, S., Jin, B., Lu, H., Zhao, S., Ding, X., Xu, L., Li, H., Liu, S., Chen, J., Chen, G."Heparanase inhibitor OGT 2115 induces prostate cancer cell apoptosis via the downregulation of MCL‑1". Oncology Letters 27, no. 2 (2024): 83. https://doi.org/10.3892/ol.2024.14217