Display options
Cite
Lee JY, Kuo CW, Tsai SL, et al. Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells. Front Pharmacol. 2016;7:81doi: 10.3389/fphar.2016.00081.
Lee, J. Y., Kuo, C. W., Tsai, S. L., Cheng, S. M., Chen, S. H., Chan, H. H., Lin, C. H., Lin, K. Y., Li, C. F., Kanwar, J. R., Leung, E. Y., Cheung, C. C., Huang, W. J., Wang, Y. C., & Cheung, C. H. (2016). Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells. Frontiers in pharmacology, 781. https://doi.org/10.3389/fphar.2016.00081
Lee, Jane Ying-Chieh, et al. "Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells." Frontiers in pharmacology vol. 7 (2016): 81. doi: https://doi.org/10.3389/fphar.2016.00081
Lee JY, Kuo CW, Tsai SL, Cheng SM, Chen SH, Chan HH, Lin CH, Lin KY, Li CF, Kanwar JR, Leung EY, Cheung CC, Huang WJ, Wang YC, Cheung CH. Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells. Front Pharmacol. 2016 Mar 31;7:81. doi: 10.3389/fphar.2016.00081. eCollection 2016. PMID: 27065869; PMCID: PMC4814469.
Copy Download .nbib Format: NLM
Share it on

Front Pharmacol. 2016 Mar 31;7:81. doi: 10.3389/fphar.2016.00081. eCollection 2016.

Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells.

Frontiers in pharmacology

Jane Ying-Chieh Lee, Ching-Wen Kuo, Shing-Ling Tsai, Siao Muk Cheng, Shang-Hung Chen, Hsiu-Han Chan, Chun-Hui Lin, Kun-Yuan Lin, Chien-Feng Li, Jagat R Kanwar, Euphemia Y Leung, Carlos Chun Ho Cheung, Wei-Jan Huang, Yi-Ching Wang, Chun Hei Antonio Cheung

Affiliations

  1. Department of Pharmacology, College of Medicine, National Cheng Kung University Tainan, Taiwan.
  2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University Tainan, Taiwan.
  3. Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center Liouying, Tainan, Taiwan.
  4. Department of Pathology, Chi-Mei Medical Center, Yung Kang District Tainan, Taiwan.
  5. Nanomedicine-Laboratory of Immunology and Molecular Biology, Faculty of Health, School of Medicine, Deakin University Waurn Ponds, Geelong, VIC, Australia.
  6. Auckland Cancer Society Research Centre and Department of Molecular Medicine and Pathology, University of Auckland Auckland, New Zealand.
  7. School of Biological Sciences, Faculty of Science, University of Auckland Auckland, New Zealand.
  8. Graduate Institute of Pharmacognosy, Taipei Medical University Taipei, Taiwan.
  9. Department of Pharmacology, College of Medicine, National Cheng Kung UniversityTainan, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityTainan, Taiwan.

PMID: 27065869 PMCID: PMC4814469 DOI: 10.3389/fphar.2016.00081

Abstract

SAHA is a class I HDAC/HDAC6 co-inhibitor and an autophagy inducer currently undergoing clinical investigations in breast cancer patients. However, the molecular mechanism of action of SAHA in breast cancer cells remains unclear. In this study, we found that SAHA is equally effective in targeting cells of different breast cancer subtypes and tamoxifen sensitivity. Importantly, we found that down-regulation of survivin plays an important role in SAHA-induced autophagy and cell viability reduction in human breast cancer cells. SAHA decreased survivin and XIAP gene transcription, induced survivin protein acetylation and early nuclear translocation in MCF7 and MDA-MB-231 breast cancer cells. It also reduced survivin and XIAP protein stability in part through modulating the expression and activation of the 26S proteasome and heat-shock protein 90. Interestingly, targeting HDAC3 and HDAC6, but not other HDAC isoforms, by siRNA/pharmacological inhibitors mimicked the effects of SAHA in modulating the acetylation, expression, and nuclear translocation of survivin and induced autophagy in MCF7 and MDA-MB-231 cancer cells. Targeting HDAC3 also mimicked the effect of SAHA in up-regulating the expression and activity of proteasome, which might lead to the reduced protein stability of survivin in breast cancer cells. In conclusion, this study provides new insights into SAHA's molecular mechanism of actions in breast cancer cells. Our findings emphasize the complexity of the regulatory roles in different HDAC isoforms and potentially assist in predicting the mechanism of novel HDAC inhibitors in targeted or combinational therapies in the future.

Keywords: HDAC; SAHA; XIAP; breast cancer; survivin

References

  1. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3578-88 - PubMed
  2. Cancer Treat Rev. 2013 Nov;39(7):802-11 - PubMed
  3. J Biol Chem. 2008 Feb 8;283(6):3289-96 - PubMed
  4. Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14015-6 - PubMed
  5. Cancer Chemother Pharmacol. 2010 Nov;66(6):1131-40 - PubMed
  6. EMBO J. 2013 Aug 14;32(16):2204-16 - PubMed
  7. Cancer Biol Ther. 2010 May 1;9(9):717-24 - PubMed
  8. J Cell Sci. 2001 Oct;114(Pt 20):3619-29 - PubMed
  9. J Histochem Cytochem. 2000 Feb;48(2):251-8 - PubMed
  10. Oncogene. 2002 Apr 18;21(17):2613-22 - PubMed
  11. Cancer Res. 1998 Dec 1;58(23):5315-20 - PubMed
  12. Nature. 1998 Dec 10;396(6711):580-4 - PubMed
  13. Clin Cancer Res. 2001 Apr;7(4):971-6 - PubMed
  14. J Cell Biol. 2003 Nov 24;163(4):789-99 - PubMed
  15. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13791-6 - PubMed
  16. Mol Cell. 2005 May 27;18(5):601-7 - PubMed
  17. Cancer Cell Int. 2010 Oct 01;10:36 - PubMed
  18. J Biol Chem. 2013 Jan 18;288(3):1603-11 - PubMed
  19. Cancer Lett. 2011 Mar 1;302(1):29-36 - PubMed
  20. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11700-5 - PubMed
  21. BMC Cancer. 2010 Jan 12;10:11 - PubMed
  22. Br J Pharmacol. 2008 Feb;153(4):657-68 - PubMed
  23. Mol Cell Biol. 2006 Dec;26(24):9220-31 - PubMed
  24. Int J Med Sci. 2012;9(10):881-93 - PubMed
  25. J Biol Chem. 2012 Mar 30;287(14):10885-93 - PubMed
  26. Oncogene. 2003 Nov 24;22(53):8581-9 - PubMed
  27. Apoptosis. 2004 Sep;9(5):583-9 - PubMed
  28. PLoS One. 2013 Jul 26;8(7):e69964 - PubMed
  29. Br J Pharmacol. 2015 Jan;172(1):214-34 - PubMed
  30. Nat Rev Mol Cell Biol. 2005 Jun;6(6):505-10 - PubMed
  31. Cell Biochem Biophys. 2013;67(3):1379-89 - PubMed
  32. PLoS One. 2015 Jul 02;10 (7):e0131771 - PubMed
  33. J Biol Chem. 2010 Nov 12;285(46):36129-37 - PubMed

Publication Types