Induction of apoptosis in the prostate by alpha1-adrenoceptor antagonists: a novel effect of "old" drugs.
Advances in our understanding of the integrated functions governing prostate cell proliferation and cell death imply that effective therapies for prostate neoplasia should not only be molecularly targeted, but should be customized to take into account the delicate balance of opposing growth influences. Evidence from studies on the dynamics of prostate growth in benign prostatic hyperplasia (BPH) and prostate cancer established that disruption of the molecular mechanisms that regulate apoptosis and cell proliferation among the stroma and epithelial cell populations may underlie the neoplastic development that characterizes the aging gland. Our own efforts have been focused on investigating whether a1-adrenoceptor antagonists clinically used for the relief of the obstructive symptoms associated with BPH affect prostate pathophysiology via mechanisms other than smooth muscle contraction. Such efforts led to the identification of a novel effect of two alpha1-adrenoceptor antagonists, doxazosin and terazosin. More recent in vitro experiments examined the potential anti-tumor action of three clinically used alpha1-adrenoceptor antagonists--doxazosin, terazosin and tamsulosin--against prostate cancer cell growth. These findings demonstrate the ability of doxazosin and terazosin, but not tamsulosin, to suppress prostate growth by inducing apoptosis among the epithelial cells in the benign and malignant prostate. Thus, evidence indicates that rather than just causing pure relaxation of the smooth muscle, certain alpha1-blockers can also affect the dynamics of prostate growth by changing the balance between prostate cell proliferation and apoptosis at the expense of the proliferative process.
Kyprianou
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Division of Urology and the Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201, USA. NKyprianou@smail.umaryland.edu
Jacobs
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SC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D017292:Doxazosin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000317:Adrenergic alpha-Antagonists; C041226:Terazosin; D017292:Doxazosin; D011224:Prazosin