Open Access

Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway

  • Authors:
    • See‑Hyoung Park
    • Jongsung Lee
    • Mi‑Ae Kang
    • Kyu Yun Jang
    • Jung Ryul Kim
  • View Affiliations

  • Published online on: April 20, 2018     https://doi.org/10.3892/ol.2018.8547
  • Pages: 9687-9696
  • Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The outcome of chemotherapy for osteosarcoma have improved during the past decade and more patients have access to combination chemotherapy, but there has been no significant clinical progress in the patient survival rate. Recently, forkhead‑box O3 (FOXO3) was identified as a pivotal transcription factor responsible for the transcriptional regulation of genes associated with suppression of cancer. The purpose of the present study was to screen small chemicals activating FOXO3 and elucidate their underlying mechanism. Using a drug discovery platform based on the phosphorylation status of FOXO3 in osteosarcoma cells, mitoxantrone (MTZ), a type of DNA‑damaging agent, was selected as a possible FOXO3 activator from the food and drug administration‑approved drug library. MTZ treatments significantly inhibited the phosphorylation level of Akt‑pS473 and caused nuclear localization of FOXO3 in osteosarcoma cells. MTZ treatment inhibited proliferation in osteosarcoma cells in vitro, whereas silencing FOXO3 potently attenuates MTZ‑mediated apoptosis in osteosarcoma cells. Taken together, the results indicated that MTZ induces apoptosis in osteosarcoma cells through an Akt/FOXO3‑dependent mechanism.
View Figures
View References

Related Articles

Journal Cover

June-2018
Volume 15 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Park SH, Lee J, Kang MA, Jang KY and Kim JR: Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway. Oncol Lett 15: 9687-9696, 2018
APA
Park, S., Lee, J., Kang, M., Jang, K.Y., & Kim, J.R. (2018). Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway. Oncology Letters, 15, 9687-9696. https://doi.org/10.3892/ol.2018.8547
MLA
Park, S., Lee, J., Kang, M., Jang, K. Y., Kim, J. R."Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway". Oncology Letters 15.6 (2018): 9687-9696.
Chicago
Park, S., Lee, J., Kang, M., Jang, K. Y., Kim, J. R."Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway". Oncology Letters 15, no. 6 (2018): 9687-9696. https://doi.org/10.3892/ol.2018.8547