Therapeutic Approaches Targeting Prostate Cancer Progression Using Novel Voltage-Gated Ion Channel Blockers

Sikes, Robert A.; Walls, Alison M.; Brennen, W. Nathaniel; Anderson, James D.; Choudhury-Mukherjee, Indrani; Schenck, Hilary A.; Brown, Milton L.

doi:10.3816/cgc.2003.n.028

Cited by 28 publications

(22 citation statements)

References 59 publications

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“…Indeed, VGSC blockers have recently been used to inhibit hormone-insensitive CaP. 46,[48][49][50] (iii) This functional role is consistent with Na v 1.7 upregulation being an early event in disease progression. (iv) The contributions of the VGSC activity to metastatic cell behaviour is such as to account for a significant part of the difference between slow and fast progressing tumours-a major problem in CaP management.…”

Section: Discussionmentioning

confidence: 79%

A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo

Diss

Stewart

Pani

et al. 2005

Prostate Cancer Prostatic Dis

143

125

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Section: Discussionmentioning

confidence: 79%

A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo

Diss

Stewart

Pani

et al. 2005

Prostate Cancer Prostatic Dis

143

125

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“…Interestingly, of the vast potassium channel family, only a few have been identified that alter cell proliferation (24)(25)(26). These include Kv1.3 and K Ca 3.1, which are particularly important for the regulation of proliferation in lymphocytes, along with Kv11.1 (HERG), Kv10.1 (Eag1), and K 2P 9.1 (TASK-3).…”

Section: Discussionmentioning

confidence: 99%

TREK-1 Is a Novel Molecular Target in Prostate Cancer

Voloshyna¹,

Besana²,

Castillo

et al. 2008

Cancer Research

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TREK-1 is a two-pore domain (K 2P ) potassium channel that carries a leak current that is time-and voltage-independent. Recently, potassium channels have been related to cell proliferation and some K 2P family channels, such as TASK-3, have been shown to be overexpressed in specific neoplasms. In this study, we addressed the expression of TREK-1 in prostatic tissues and cell lines, and we have found that this potassium channel is highly expressed in prostate cancer but is not expressed in normal prostate nor in benign prostatic hyperplasia. Furthermore, expression of TREK-1 correlates strongly with the grade and the stage of the disease, suggesting a causal link between channel expression and abnormal cell proliferation. In vitro studies showed that TREK-1 is highly expressed in PC3 and LNCaP prostate cancer cell lines but is not detectable in normal prostate epithelial cells (NPE). In this report, we show that overexpression of TREK-1 in NPE and Chinese hamster ovary (CHO) cells leads to a significant increase in proliferation. Moreover, the increased cell proliferation rate of PC3 cells and TREK-1 overexpressing CHO cells could be reduced when TREK-1 current was reduced by overexpression of a dominant-negative TREK-1 mutant or when cells were exposed to a TREK-1 inhibitor. Taken together, these data suggest that TREK-1 expression is associated with abnormal cell proliferation and may be a novel marker for and a molecular target in prostate cancer.

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“…These studies utilized ion channel agonists and antagonists to manipulate the functional state of the channel in cells to determine the effects of channel activity on cancer cell behavior. Our laboratories are in the process of synthesizing and testing potent, selective, voltagesensitive ion channel (VSIC) antagonists for use as tumoristatic or tumoricidal agents [2,6].…”

Section: Introductionmentioning

confidence: 99%

Voltage-sensitive ion channels and cancer

Fiske

Fomin

Brown

et al. 2006

Cancer Metastasis Rev

Self Cite

126

103

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Plasma membrane voltage-sensitive ion channels classically have been associated with a variety of inherited diseases or "channelopathies" that range in the severity of symptoms from mild to lethal. Ion channels are found throughout the body and are responsible for facilitated diffusion of ions down the electrochemical gradient across cells membranes in various tissues. Voltage-sensitive ion channels open in response to changes in the membrane potential and are primarily found in excitable cells and tissues. Potassium, calcium, and sodium channels play critical roles in the development of major diseases, such as hyperkalemia, epilepsy, congenital myotonia and several cardiac arrythmias. Recently, cancer studies have begun to define the role of voltage-sensitive ion channels in the progression of cancer to a more malignant phenotype. In cancer, the increased expression or increased kinetics of voltage-sensitive ion channels is associated with an increasing malignant potential as evinced by their role in cell proliferation, migration and survival; as such, these channels are becoming the targets of significant drug development efforts to block or reduce voltage-sensitive ion channel activity in order to prevent or combat malignant disease.

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Therapeutic Approaches Targeting Prostate Cancer Progression Using Novel Voltage-Gated Ion Channel Blockers

Cited by 28 publications

References 59 publications

A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo

A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo

TREK-1 Is a Novel Molecular Target in Prostate Cancer

Voltage-sensitive ion channels and cancer

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