Home
Resources
Publications
Prazosin but Not Tamsulosin Sensitises PC-3 and LNCaP Prostate Cancer Cells to Docetaxel

Prazosin but Not Tamsulosin Sensitises PC-3 and LNCaP Prostate Cancer Cells to Docetaxel

Briohny H Spencer, Catherine M McDermott, Russ Chess-Williams, David Christie, Shailendra Anoopkumar-Dukie

Pharmacology. 2018 Apr 17;102(1-2):10-18.

PMID: 29669348

Abstract:

Background/aims:
Docetaxel is currently the first-line chemotherapeutic agent available for the treatment of patients with advanced prostate cancer (PCa). While docetaxel has been shown to modestly improve survival times for patients; they also experience significant docetaxel-induced toxicities. If treatment failure occurs, there are currently limited alternatives that show survival benefits for patients and therefore there is an urgent need for adjunct therapies. Some quinazoline-based alpha1-adrenoceptor (ADR) antagonists have previously been shown to have cytotoxic actions in PCa cells, but there is no research into their effects on docetaxel-induced toxicity. Therefore, the aim of this study was to determine if the quinazoline ADR, prazosin influenced the sensitivity of PCa cells to docetaxel in vitro. We hypothesised that prazosin, but not tamsulosin, in combination with docetaxel would possess synergistic cytotoxic actions on PC-3 and LNCaP PCa cells.
Methods:
PC-3 and -LNCaP cells were pre-treated (1 h) with prazosin (30 µmol/L) or tamsulosin (30 µmol/L), followed by docetaxel (12.5-100 μmol/L) for 24 h. Docetaxel-induced toxicity was measured in terms of changes in cell proliferation, autophagy, apoptosis and the production of reactive oxygen species (ROS).
Results:
Prazosin sensitised both cell lines (PC-3 and LNCaP) to docetaxel-induced toxicity. This effect appears to be mediated by autophagy and may also involve apoptosis. These sensitising effects of prazosin appear to be largely independent of ROS production. In contrast, tamsulosin did not affect docetaxel-induced toxicity.
Conclusion:
We have shown for the first time that prazosin increases docetaxel-induced toxicity in PC-3 and LNCaP cells. Prazosin may therefore offer a viable treatment option in combination with docetaxel in metastatic PCa.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP19237844-A	Prazosin hydrochloride		19237-84-4	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: