α1-adrenoceptor agonists have recently been recognized as growth factors for several cell types, including both stromal smooth muscle- and epithelial cells of the prostate gland, by triggering off a cascade of intracellular signal transduction pathway that controls cell proliferation. On the contrary, quinazoline α1 -blockers (doxazosin, terazosin, prazosin) inhibit cell kinetics and induce, above all, anoikis and apoptotic death of both stromal smooth muscle- and epithelial cells, through α1 -adrenoceptor-indipendent mechanisms, thus preventing or delaying prostate tumor growth.
PouyssegurJ., SeuwenK.Transmembrane receptors and intracellular pathways that control cell proliferation. Annu Rev Physiol1992; 54: 195–210.
2.
BoeschS.T., CorvinS., ZhangJ., RogatschH., BartschG., KlockerH.Modulation of the differentiation status of cultured prostatic smooth muscle cells by an alpha-adrenergic receptor antagonist. Prostate1999; 39: 226–33.
3.
KretzschmarM., DoodyJ., MassagueJ.Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator. Smad-l. Nature1997; 389: 618–22.
4.
KyprianouN.Tissue proliferation: differential effects of adrenergic agents. In Textbook of benign prostatic hyperplasia, 2nd ed.FizpatrickJ. (Ed). Oxford, UK, ISIS Medical Media2000, pp. 14–18.
5.
JacobsS.C., StoryM.T.Exocrine secretion of EGF by the rat prostate: effect of adrenergic agents, cholinergic agents and VIP. Prostate1988; 13: 79–87.
6.
SimpsonP.C.Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha-1 adrenergic response. J Clin Invest1983; 72: 732–8.
7.
YuS.M., TsaiS.Y., GuhJ.H., KoF.N., TengC.M., OuJ.T.Mechanism of catecholamine-induced proliferation of vascular smooth muscle cells. Circulation1996; 94: 547–54.
SmithP., RoadesN.P., BeesleyC., KeX., FosterC.S.Prostatic stromal cell phenotype is directly modulated by norepinephrine. Urology1998; 663–70.
10.
LinV.K., BenainE.A., McConnellJ.D.Alpha-blokade down-regulates myosine chain gene expression in human BPH. Urology2001; 57: 170–5.
11.
SmithP., RoadesN.P., KeX., FosterC.S.Influence of the alpha-1 adrenergic antagonist, doxazosin, on noradrenaline-induced modulation of cytoskeletal proteins. The Prostate1999; 38: 216–27.
12.
SchalkenJ.A.Apoptosi nella prostata umana. Drugs today2001; 57: 23–26.
13.
KyprianouN., LitvakJ.P., BorkowskyA., AlexanderR., JacobsS.C.Induction of prostate apoptosis by doxazosin in BPH. J Urol1998; 159: 1810–15.
14.
YangG., TimmeT., ParkS.H., WuX., WyllieM.G., ThompsonT.C.TGF-beta transduced mouse prostate reconstitutions: induction of apoptosis by doxasosin. Prostate1997; 33: 157.
15.
BenningC.M., KyprianouN.Quinazoline-derived α1-adrenoceptor antagonists induce cancer cell apoptosis via adrenoceptor-indipendent action. Cancer Res2002; 62: 597–603.
16.
KyprianouN., BenningC.M.Suppression of human prostate cancer cell growth by alpha-1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis. Cancer Res2000; 60: 4550–5.
17.
ChonJ.K., BorkoswkiA., PartinA.W., IsaacsJ.T., JacobsS.C., KyprianouN.Alpha-1-adrenoceptor antagonists doxazosin and terazosin induce prostate apoptosis without affecting cell proliferation in patients whith benign prostatic hyperplasia. J Urol1999; 161: 2002–8.
18.
CalC., UsluR., GunaydinG., OzyurtC., OmayS.B.Doxazosin: a new cytotoxic agent for prostate cancer?BJU International2000; 85: 672–5.
19.
ThatteU., DahanukarS.Apoptosis: clinical relevance and pharmacological manipulation. Drugs1997; 54: 511–532.
20.
WaldenP.D., GlobinaY., NiederA.Induction of anoikis by doxazosin in prostate cancer cells. Urol Res2004; 32: 261–5.
21.
KyprianouN.Doxazosin and terazosin suppress prostate growth by inducing apoptosis; clinical significance. J Urol2003; 169: 1520–5.
22.
ZhuB., KyprianouN.Transforming growth factor-β and prostate cancer. Cancer Treat Res2005; 126. 157–73.
23.
CecchiM., Di BenedettoA., SummontiD.Confronto tra prazosina, terazosina, tamsulosina: studio funzionale e di legame su tessuti isolati umani prostatici e vascolari. Minerva Urol Nefrol2002; 54: 193–8.
24.
KimI.Y., AhnH.J., ZelnerD.J., ShawJ.W., SensibarJ.A., KimJ.H.Genetic change in TGF-beta in human prostate cancer cells. Cancer Res1996; 56: 44–8.
KeledjianK., KyprianouN.Anoikis induction by quinazoline-based α1-adrenoceptor antagonists in prostate cancer cells: antagonistic effect of bcl-2. J Urol2003; 169: 1150–5.
27.
MiyazakiT., ShenM., FujikuraD., TosaN., KimH.R., ZonS.Functional role of death-associated protein-3 (DAP3) in anoikis. J Biol Chem2004; 279: 44667–72.
28.
KothakotaS., AzumaT., ReinhartC., KlippelA., TangJ., ChuK.Caspase-3-generated fragment of gelsonin: effector of morphological change in apoptosis. Science1997; 278, 294–7.
29.
EarnshawW.C., MartinsL.M., KaufmannS.H.Mammalian caspases structure, activation, substrates and functions during apoptosis. Annu Rev Biochem1999; 68: 383–90.
30.
FrischS.M.Evidence for a function of death-receptor-related, death-domain containing proteins in anoikis. Curr Biol1999; 9: 1047–50.
ZhanM., ZhaoH., HanZ.C.Signalling mechanisms of anoikis. Histol Histopathol2004; 19: 973–83.
33.
WenL.P., FahrniJ.A., TroieS., GuanJ.L., OrthK., RosenG.D.Cleavage of focal adhesion kinase by caspases during apoptosis. J Biol Chem1997; 272: 26056–60.
34.
SlackJ.K., AdamsR.B., RovinJ.D., BissonetteE.A., StokerC.E., ParsonJ.T.Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene2001; 20: 1152–8.
35.
LubjanM., FerrueloA., PaezA., MorenoA., BerenguerA.Prostate apoptosis after doxazosin treatment in the spontaneous hypertensive rat model. BJU International2004, 93, 410–4.
36.
GlassmanD.T., ChonJ., BarkowskiA., JacobsS.C., KiprianouN.Combined effects of terazosin and finasteride on apoptosis, cell proliferation, TGF-β expression in benign prostatic hyperplasia. Prostate2001; 45: 45–51.
37.
WindhamT.C., ParikhN.U., SiwakD.R., SummyJm, McConkeyDJ, KrakerA.J., GallickG.E.Src activation regulates anoikis in human colon tumor cell lines. Oncogene2002; 21: 7797–807.
38.
HouY., WongE., MartinJ., SchoenleinP.V., DostmannW.R., BrowingD.D.A role for cyclic-GMP dependent protein kinase in anoikis. Cell Signal2005; 8: 410–8.
39.
TahmatzopulosA., ShengS., KyprianouN.Maspin sensitizes prostate cancer cells to doxazosin-induced apoptosis. Oncogene2005; 24: 5375–83.
40.
Sebolt-LeopoldJ.S., HerreraR.Targeting the MAPKs cascade to treat cancer. Nature Rev Cancer2004; 4: 937–47.
41.
ArkinM.R., WellsJ.A.Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov2004; 3: 301–17.
42.
McKenzieS., KyprianouN.Apoptosis evasion: the role of survival pathways in prostate cancer progression and therapeutic resistance. J Cell Biochem2005; 200: 217–27.
