Glyceryl trinitrate‑induced cytotoxicity of docetaxel‑resistant prostatic cancer cells is associated with differential regulation of clusterin

  • Authors:
    • Sarra Bouaouiche
    • Lea Magadoux
    • Lucile Dondaine
    • Sylvie Reveneau
    • Nicolas Isambert
    • Ali Bettaieb
    • Jean‑François Jeannin
    • Veronique Laurens
    • Stephanie Plenchette
  • View Affiliations

  • Published online on: February 1, 2019     https://doi.org/10.3892/ijo.2019.4708
  • Pages: 1446-1456
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Metastatic castration resistant prostate cancer (mCRPC) relapse due to acquired resistance to chemotherapy, such as docetaxel, remains a major threat to patient survival. Resistance of mCRPC to docetaxel can be associated with elevated levels of soluble clusterin (sCLU) and growth differentiation factor‑15 (GDF‑15). Any strategies aiming to modulate sCLU and/or GDF‑15 in docetaxel‑resistant prostate cancer cells present a therapeutic interest. The present study reports the cytotoxic effect of a nitric oxide donor, glyceryl trinitrate (GTN), on docetaxel‑resistant mCRPC human cell lines and demonstrates that GTN displays greater inhibition of cell viability toward docetaxel‑resistant mCRPC cells than on mCRPC cells. It is also demonstrated that GTN modulates the level of expression of clusterin (CLU) which is dependent of GDF‑15, two markers associated with docetaxel resistance in prostate cancer. The results indicate that GTN represses the level of expression of the cytoprotective isoform of CLU (sCLU) and can increase the level of expression of the cytotoxic isoform (nuclear CLU) in docetaxel resistant cells. Furthermore, it was observed that GTN differentially regulates the level of the precursor form of GDF‑15 between resistant and parental cells, and that recombinant GDF‑15 can modulate the expression of CLU isoforms and counteract GTN‑induced cytotoxicity in resistant cells. A link was established between GDF‑15 and the expression of CLU isoforms. The present study thus revealed GTN as a potential therapeutic strategy to overcome docetaxel‑resistant mCRPC.
View Figures
View References

Related Articles

Journal Cover

April-2019
Volume 54 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Bouaouiche S, Magadoux L, Dondaine L, Reveneau S, Isambert N, Bettaieb A, Jeannin JF, Laurens V and Plenchette S: Glyceryl trinitrate‑induced cytotoxicity of docetaxel‑resistant prostatic cancer cells is associated with differential regulation of clusterin. Int J Oncol 54: 1446-1456, 2019
APA
Bouaouiche, S., Magadoux, L., Dondaine, L., Reveneau, S., Isambert, N., Bettaieb, A. ... Plenchette, S. (2019). Glyceryl trinitrate‑induced cytotoxicity of docetaxel‑resistant prostatic cancer cells is associated with differential regulation of clusterin. International Journal of Oncology, 54, 1446-1456. https://doi.org/10.3892/ijo.2019.4708
MLA
Bouaouiche, S., Magadoux, L., Dondaine, L., Reveneau, S., Isambert, N., Bettaieb, A., Jeannin, J., Laurens, V., Plenchette, S."Glyceryl trinitrate‑induced cytotoxicity of docetaxel‑resistant prostatic cancer cells is associated with differential regulation of clusterin". International Journal of Oncology 54.4 (2019): 1446-1456.
Chicago
Bouaouiche, S., Magadoux, L., Dondaine, L., Reveneau, S., Isambert, N., Bettaieb, A., Jeannin, J., Laurens, V., Plenchette, S."Glyceryl trinitrate‑induced cytotoxicity of docetaxel‑resistant prostatic cancer cells is associated with differential regulation of clusterin". International Journal of Oncology 54, no. 4 (2019): 1446-1456. https://doi.org/10.3892/ijo.2019.4708