Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines.
Prostate
; 76(8): 757-66, 2016 Jun.
Article
in En
| MEDLINE
| ID: mdl-26880388
ABSTRACT
BACKGROUND:
Some α1 -adrenoceptor antagonists possess anti-cancer actions that are independent of α1 -adrenoceptors and the aim of these studies was to assess the relative cytotoxic potencies of α1 -adrenoceptor antagonists and the mechanisms involved in these actions.METHODS:
PC-3 and LNCap human prostate cancer cells were exposed to α1 -adrenoceptor antagonists (0.01-100 µM) and cell survival assessed after 24-72 hr. The levels of apoptosis, autophagy and stress related proteins were also determined.RESULTS:
The relative cytotoxic potency order was prazosin = doxazosin > terazosin = silodosin = alfuzosin > tamsulosin on both cell types, but LNCaP cells were significantly more sensitive to these effects than PC-3 cells. Prazosin and doxazosin increased levels of apoptotsis and autophagy in both cell lines, and activated EphA2 receptors in PC-3 cells. Autophagy contributed to survival of LNCaP, but promoted cell death in PC-3 cells. Treatment with prazosin (30 µM) altered the expression of several cell stress-related proteins elevating phospho-p38α and reducing S6 kinase in both cell lines. Surprisingly some proteins were differentially affected in the two prostate cancer cell lines Akt and p27 increasing and HIF-1α decreasing in LNCap cells but not PC-3, while ADAMTS1 was increased in PC-3 cells only.CONCLUSIONS:
Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
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Autophagy
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Cell Death
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Apoptosis
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Adrenergic alpha-1 Receptor Antagonists
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Antineoplastic Agents
Limits:
Humans
/
Male
Language:
En
Journal:
Prostate
Year:
2016
Type:
Article
Affiliation country:
Australia