Antitumor Action of a₁-Adrenoceptor Blockers on Human Bladder, Prostate and Renal Cancer Cells

Abstract

The present study investigated the antitumor action of α₁-adrenoceptor blockers on human bladder, prostate and renal cancer cells. For bladder cancer cell lines used here such as 253J, 5637, KK-47, T24 and UM-UC-3 cells, prazosin, a selective α₁-adrenoceptor blocker, reduced cell viability at concentrations more than 30 µmol/l. Likewise, naftopidil, a blocker of α_1A- and α_1D-adrenoceptors, reduced cell viability for all the bladder cancer cells used here in a concentration (10–100 µmol/l)-dependent manner, with a much greater advantage than prazosin. Naftopidil also reduced cell viability for human prostate cancer cell lines such as DU145, LNCap and PC-3 cells and ACHN human renal cancer cells, with a much higher potential than prazosin. Thus, the results of the present study suggest that naftopidil could be a beneficial antitumor drug for the treatment of urological cancers.

1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol as a Potential Anticancer Drug

“…Naftopidil has been shown to inhibit prostate cancer cell growth by arresting the G 1 phase of cell cycling [2,3]. In our studies, naftopidil reduced cell viability for bladder, prostate, and renal cancer cell lines [4] or induced apoptosis in malignant mesothelioma cell lines [5]. These findings raise the possibility that naftopidil might be useful as an anticancer drug.…”

A prospective randomized controlled study on the Suppression of Prostate Cancer by Naftopidil (SNAP)

“…Furthermore, we confirmed that naftopidil induced apoptosis in prostatic cancer cell lines and human prostatic cancer tissues via inhibition of Smad2 phosphorylation-medicated transforming growth factor (TGF) beta activation [10]. Other inhibitory mechanisms proposed include activation of death receptors [11] and blocking tubulin formation [12]. The anti-proliferative effects of naftopidil on cell growth have been reported for human renal cancer cells, bladder cancer, cervical cancer, and malignant pleural mesothelioma [10,[13][14][15][16].…”

A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility “in vitro”

“…As expected, the antiproliferative action of the compound in PC3 cells maintained in growth-stimulating conditions (FCS 10%) is still dose-dependent, but less effective, with a mean reduction of cell proliferation of 18 and 37% at doses of 25 and 50 μM, respectively. In these culture conditions, A175 seems to have a reduced potency compared to less specific alpha1-AR antagonists [9,27] or to other selective alpha1D-AR blockers [11,29], the IC50 of which ranges from 2 to 30 μM. However, doxazosin, terazosin, as well as naftopidil and its related compounds, reduce the growth rate also of DU145 and LNCaP cells [26,27,29], which, as previously discussed, lack alpha1D-ARs.…”

“…In these culture conditions, A175 seems to have a reduced potency compared to less specific alpha1-AR antagonists [9,27] or to other selective alpha1D-AR blockers [11,29], the IC50 of which ranges from 2 to 30 μM. However, doxazosin, terazosin, as well as naftopidil and its related compounds, reduce the growth rate also of DU145 and LNCaP cells [26,27,29], which, as previously discussed, lack alpha1D-ARs. It might be possible that all these compounds act either by interacting with other AR subtypes, or through an AR-independent mechanism, as suggested by many authors [9,18,25,28].…”

“…alpha1A-AR antagonists (naftopidil [13,[26][27][28] and its very recent amide-indole derivatives [29]), or markedly alpha1D-AR antagonists (clopenphendioxan [11] and gem-diphenyl dioxane derivatives [30,31]). On the other hand, very potent, but not subtype-specific alpha1-AR blockers, such as WB4101, or also other alpha1D-AR selective antagonists, such as BMY-7378, do not exhibit significant antiproliferative effect on PC cells [14,30].…”