Verapamil Inhibits Proliferation of LNCaP Human Prostate Cancer Cells Influencing K<sup>+</sup> Channel Gating

Rybalchenko, Volodymyr; Prevarskaya, Natalia; Coppenolle, Fabien Van; Legrand, Guillaume; Lemonnier, Loïc; Bourhis, Xuefen Le; Skryma, Roman

doi:10.1124/mol.59.6.1376

Cited by 58 publications

(34 citation statements)

References 34 publications

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“…In addition, inhibition of delayed-rectifier channels of the Kv protein family by antagonists such as TEA or 4-AP alters cell growth in various tumor cell types (Pancrazio et al, 1993;Rouzaire-Dubois and Dubois, 1998;Rybalchenko et al, 2001). Consistent with these observations, we show here that TEA and 4-AP, but not the hSK channel blocker apamin, inhibit both the VOK current and cell growth in Jurkat cells.…”

Section: Discussionsupporting

confidence: 78%

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K⁺ Channel Inhibition and p27^kip1 Accumulation

Renaudo¹,

Watry²,

Chassot³

et al. 2004

J Pharmacol Exp Ther

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Previous studies have shown that receptors are overexpressed in tumor cells. However, the role of receptors remains enigmatic. Recently, we and others have demonstrated that -1 receptor modulates K ϩ channels in pituitary. In the present report, patch-clamp and Western blot assays were used in small cell lung cancer (SCLC, NCI-H209, and NCI-H146) and leukemic (Jurkat) cell lines to investigate the effects of ligands on voltage-gated K ϩ channels and cell proliferation. The ligands (ϩ)-pentazocine, igmesine, and 1,3-di(2-tolyl)guanidine (DTG) all reversibly inhibited voltage-activated K ϩ currents in both cell lines. The potency of ligand-induced inhibition (10 M) was igmesine ϭ (ϩ)-pentazocine Ͼ DTG, pointing to the involvement of -1 receptors. Addition of the K ϩ channel blockers tetraethylammonium (TEA) and 4-aminopyridin or one of cited ligands in the culture media reversibly inhibited Jurkat cell growth. Interestingly, K ϩ channel blockers and ligands caused an accumulation of the cyclin-dependent kinase inhibitor p27 kip1 and a decrease in cyclin A expression in Jurkat and SCLC cells, whereas no effect could be detected on p21 cip1 . Moreover, ligands and TEA had no effect on caspase 3 activity. Accordingly, incubation of cells with ligands did not provoke DNA laddering. These data demonstrate that ligands and voltage-dependent channel blockers inhibit cell growth through a cell cycle arrest in the G 1 phase but not via an apoptotic mechanism. Altogether, these results indicate that the -1 receptor-induced inhibition of the cell cycle is, at least in part, the consequence of the inhibition of K ϩ channels.

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Section: Discussionsupporting

confidence: 78%

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K⁺ Channel Inhibition and p27^kip1 Accumulation

Renaudo¹,

Watry²,

Chassot³

et al. 2004

J Pharmacol Exp Ther

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“…This prolonged latency may be explained by the wash-out of some intracellular factors in conventional whole-cell configuration, such as delayers or channel activation modulators. Indeed, we had previously verified the rate of intracellular perfusion in LNCaP cells (38): it took about 3-4 minutes to replace half the cell cytoplasm solution with pipette solution. In the Fura-2 experiments, the [Ca 2+ ] i response latency was even more prolonged (at least 20 minutes).…”

Section: Discussionmentioning

confidence: 99%

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Thebault¹,

Roudbaraki²,

Sydorenko³

et al. 2003

J. Clin. Invest.

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. Y. Shuba's present address is: Bogomoletz Institute of Physiology, Kiev, Ukraine. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: α1-adrenergic receptor (α1-AR); human prostate cancer epithelial cell (hPCE cell); phospholipase C (PLC); inositol triphosphate (IP3); diacylglycerol (DAG); transient receptor potential (TRP); α1A subtype of α1-AR (α1A-AR); lymph node carcinoma of the prostate cells (LNCaP cells); intracellular Ca 2+ concentration ([Ca 2+ ]i); phenylephrine (Phe); intracellular Ca 2+ oscillations (osc); 2-aminophenyl borate (2-APB); store-operated Ca 2+ -channel (SOC); 1-oleoyl-2-acetyl-snglycerol (OAG); 1,2-dioctanoyl-sn-glycerol (DOG); extracellular Ca 2+ concentration ([Ca 2+ ]out); Phe-activated current (IPhe); current reversal potential (Erev).

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“…Recent studies on cellular models, however, have shown that calcium-channel blockers inhibit PCa cell proliferation (7)(8)(9). Rybalchenko et al showed that extracellular application of verapamil inhibits proliferation of the human PCa cell line LNCaP (8).…”

Section: Introductionmentioning

confidence: 99%

Inverse Association between Prostate Cancer and the Use of Calcium Channel Blockers

Debes

Roberts²,

Jacobson

et al. 2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Calcium channel blockers block calcium signal-mediated apoptosis. It is hypothesized that the use of these drugs may be associated with the development of cancer. This study investigated the association between daily use of calcium channel blockers and prostate cancer in a community-based cohort of men who participated in a longitudinal study of lower urinary tract symptoms. Study subjects were men ages 40 to 79 years by January 1, 1990, and were randomly selected from Olmsted County in Minnesota. At baseline, participants underwent an interview to determine all medications taken on a daily basis, including calcium channel blockers and to elicit a family history of prostate cancer. During followup, all men with a histological diagnosis of prostate cancer were identified through patient self-report and by a review of the complete medical record. Over 12,668 person years of follow-up, 15 (6.8%) of 220 calcium channel blocker users and 120 (10.5%) of 1142 nonusers developed prostate cancer (P ‫؍‬ 0.09; odds ratio, 0.62; 95% confidence interval, 0.36 -1.10). With adjustment for age and family history of prostate cancer, the risk (odds ratio, 95% confidence interval) of prostate cancer was 0.55 (0.31-0.97) in calcium channel blocker users compared with nonusers. In analyses stratified by family history of prostate cancer, the risk of prostate cancer was 0.45 (0.23-0.88) in men without a family history and 2.64 (0.82-8.47) in men with a family history of prostate cancer (P ‫؍‬ 0.006). These findings suggest an association between prostate cancer and daily use of calcium channel blockers that varies by family history of prostate cancer.

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Verapamil Inhibits Proliferation of LNCaP Human Prostate Cancer Cells Influencing K⁺ Channel Gating

Abstract: The mechanisms of verapamil and tetraethylammonium (TEA) inhibition of voltage-gated K ϩ channels in LNCaP human prostate cancer cells were studied in whole-cell and outside/insideout patch-clamp configurations. Rapidly activating outward K ϩ

Cited by 58 publications

References 34 publications

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K⁺ Channel Inhibition and p27^kip1 Accumulation

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K⁺ Channel Inhibition and p27^kip1 Accumulation

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Inverse Association between Prostate Cancer and the Use of Calcium Channel Blockers

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Verapamil Inhibits Proliferation of LNCaP Human Prostate Cancer Cells Influencing K+ Channel Gating

Abstract: The mechanisms of verapamil and tetraethylammonium (TEA) inhibition of voltage-gated K ϩ channels in LNCaP human prostate cancer cells were studied in whole-cell and outside/insideout patch-clamp configurations. Rapidly activating outward K ϩ

Cited by 58 publications

References 34 publications

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K+ Channel Inhibition and p27kip1 Accumulation

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K+ Channel Inhibition and p27kip1 Accumulation

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Inverse Association between Prostate Cancer and the Use of Calcium Channel Blockers

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Product

Resources

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Verapamil Inhibits Proliferation of LNCaP Human Prostate Cancer Cells Influencing K⁺ Channel Gating

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K⁺ Channel Inhibition and p27^kip1 Accumulation

Inhibition of Tumor Cell Proliferation by σ Ligands Is Associated with K⁺ Channel Inhibition and p27^kip1 Accumulation