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Relative Cytotoxic Potencies And Cell Death Mechanisms Of Α1-Adrenoceptor Antagonists In Prostate Cancer Cell Lines, Amanda Forbes, Shailendra Anoopkumar-Dukie, Russ Chess-Williams, Catherine M. Mcdermott
Relative Cytotoxic Potencies And Cell Death Mechanisms Of Α1-Adrenoceptor Antagonists In Prostate Cancer Cell Lines, Amanda Forbes, Shailendra Anoopkumar-Dukie, Russ Chess-Williams, Catherine M. Mcdermott
Catherine M. McDermott
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 (0.01-100μM) and cell survival assessed after 24-72hr. 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 …