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Article

Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt

  • Authors:
    • Wei Cao
    • Renhui Shen
    • Seth Richard
    • Yu Liu
    • Mohammad Jalalirad
    • Margot P. Cleary
    • Antonio B. D'Assoro
    • Sergio A. Gradilone
    • Da-Qing Yang
  • View Affiliations / Copyright

    Affiliations: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China, Mayo Clinic, Rochester, MN 55905, USA
  • Article Number: 41
    |
    Published online on: December 24, 2021
       https://doi.org/10.3892/or.2021.8252
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Abstract

Mutations of p53 tumor suppressors occur more frequently in cancers at advanced stages or in more malignant cancer subtypes such as triple‑negative breast cancer. Thus, restoration of p53 tumor suppressor function constitutes a valuable cancer therapeutic strategy. In the present study, it was revealed that a specific inhibitor of histone deacetylase 6, ACY‑1215, caused increased acetylation of p53 in breast cancer cells with mutated p53, which was accompanied by increased expression of p21. These results suggested that ACY‑1215 may lead to enhanced transcriptional activity of p53. It was also determined that ACY‑1215 treatment resulted in G1 cell cycle arrest and apoptosis in these cancer cells. Furthermore, ACY‑1215 displayed a synergistic effect with specific inhibitors of ATM, an activator of Akt, in inducing cancer cell apoptosis and inhibiting their motility. More importantly, it was observed that combination of ACY‑1215 and ATM inhibitors exhibited markedly more potent antitumor activity than the individual compound in xenograft mouse models of breast cancer with mutant p53. Collectively, our results demonstrated that ACY‑1215 is a novel chemotherapeutic agent that could restore mutant p53 function in cancer cells with strong antitumor activity, either alone or in combination with inhibitors of the ATM protein kinase.
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Copy and paste a formatted citation
Spandidos Publications style
Cao W, Shen R, Richard S, Liu Y, Jalalirad M, Cleary MP, D'Assoro AB, Gradilone SA and Yang D: Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt. Oncol Rep 47: 41, 2022.
APA
Cao, W., Shen, R., Richard, S., Liu, Y., Jalalirad, M., Cleary, M.P. ... Yang, D. (2022). Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt. Oncology Reports, 47, 41. https://doi.org/10.3892/or.2021.8252
MLA
Cao, W., Shen, R., Richard, S., Liu, Y., Jalalirad, M., Cleary, M. P., D'Assoro, A. B., Gradilone, S. A., Yang, D."Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt". Oncology Reports 47.2 (2022): 41.
Chicago
Cao, W., Shen, R., Richard, S., Liu, Y., Jalalirad, M., Cleary, M. P., D'Assoro, A. B., Gradilone, S. A., Yang, D."Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt". Oncology Reports 47, no. 2 (2022): 41. https://doi.org/10.3892/or.2021.8252
Copy and paste a formatted citation
x
Spandidos Publications style
Cao W, Shen R, Richard S, Liu Y, Jalalirad M, Cleary MP, D'Assoro AB, Gradilone SA and Yang D: Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt. Oncol Rep 47: 41, 2022.
APA
Cao, W., Shen, R., Richard, S., Liu, Y., Jalalirad, M., Cleary, M.P. ... Yang, D. (2022). Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt. Oncology Reports, 47, 41. https://doi.org/10.3892/or.2021.8252
MLA
Cao, W., Shen, R., Richard, S., Liu, Y., Jalalirad, M., Cleary, M. P., D'Assoro, A. B., Gradilone, S. A., Yang, D."Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt". Oncology Reports 47.2 (2022): 41.
Chicago
Cao, W., Shen, R., Richard, S., Liu, Y., Jalalirad, M., Cleary, M. P., D'Assoro, A. B., Gradilone, S. A., Yang, D."Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt". Oncology Reports 47, no. 2 (2022): 41. https://doi.org/10.3892/or.2021.8252
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