Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: Comparison of strongly and weakly metastatic cell lines

Fraser, Scott P.; Grimes, Julia A.; Djamgoz, Mustafa B.A.

doi:10.1002/1097-0045(20000615)44:1<61::aid-pros9>3.0.co;2-3

Cited by 88 publications

(68 citation statements)

References 50 publications

(55 reference statements)

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“…Metastatic properties of Mat-LyLu and AT-2 cells are closely associated with VGSCs, as has been demonstrated in studies on TTX, which specifically blocks VGSCs (4,7,8,11). In the present study, 200 nM TTX was used as the positive control, as it has been previously reported that TTX does not produce changes in the proliferation of either cell line even at higher doses (600 nM and 6 µM) than 200 nM (5,7,27). TTX reduced the movement distance of Mat-LyLu cells in a lateral direction, and this effect was found to be statistically significant.…”

Section: Resultsmentioning

confidence: 51%

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

Aktaş

Altun

2016

Oncology Letters

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Abstract. Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat-LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined. Tetrodotoxin was used to block the voltage-gated sodium channels (VGSCs) associated specifically with Mat-LyLu cells. Cell proliferation was detected spectrophotometrically using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The mitotic index was determined using the Feulgen staining method. Lateral motility was quantified by wound-healing assays. The results of the present study demonstrated that cell kinetics (proliferation and mitotic activity) and motility were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H. helix fruit suppressed Mat-LyLu cell migration, with no effect on proliferation. The opposite effects were observed in AT-2 cells; migration was not affected but proliferation was inhibited. In conclusion, the ethanolic fruit extract of H. helix may inhibit the cell migration of Mat-LyLu cells by blocking VGSCs. However, the effect of ethanolic leaf extract of H. helix treatment on the lateral motility of the cancer cells is unclear. IntroductionProstate cancer is the second most common cause of cancer-associated mortality among men worldwide (1). By the time prostate cancer is diagnosed, metastasis has occurred in the majority of men, as early prostate cancer has no symptoms. Metastatic diseases are a significant public health problem affecting cancer patients and their families (2). Metastasis occurs when malignant cells leave the primary tumor, migrate via the circulatory system, localize in distant areas and lead to the development of secondary tumors. It is a multistep process, and the steps are similar in all tumors. Mobilization of tumor cells is an important step in metastasis (3). Ion channels regulate, and stimulate numerous behavioral changes in cells that are associated with cancer and metastasis, including cell movement (elongation and lateral motility) (4,5), migration, galvanotaxis (6) and invasion (7,8). A number of in vitro (9-11) and in vivo (12) studies performed using tetrodotoxin (TTX), which specifically blocks voltage-gated sodium channels (VGSCs) (13), have suggested that the plasma membrane of prostate cancer cells may gain a more excitable phenotype due to increased VGSC expression, and thus malignancy is able to progress. Bennett et al (11) demonstrated that VGSC expression was 'necessary' and 'enough' for the invasiveness of prostate cancer cells. Prostate cancer tends to invade the bones, lungs and lymph nodes (14). Combating metastasis formation and growth are important for succ...

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Section: Resultsmentioning

confidence: 51%

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

Aktaş

Altun

2016

Oncology Letters

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“…6,40 Briefly, for proliferation, cells were plated in 35 mm Falcon tissue culture dishes at an initial density of 3 Â 10 4 cells/dish and allowed to settle overnight. Each cell line was then incubated in 0.8 ml normal growth medium with or without the added drug for 48 h, with an identical solution change at 24 h. Proliferation was quantified using the colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.…”

Section: Proliferation and Toxicity Assaysmentioning

confidence: 99%

“…We have shown previously that TTX (p6 mM) is not toxic and does not have an effect on the proliferation of PCa cells. 40 …”

Section: Proliferation and Toxicity Assaysmentioning

confidence: 99%

Notch signalling and voltage-gated Na+ channel activity in human prostate cancer cells: independent modulation of in vitro motility

Scorey

Fraser

Patel

et al. 2006

Prostate Cancer Prostatic Dis

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“…Available data provides evidence that an application of a specific inhibitor of Kv1.3 channels, margatoxin (MgTX), significantly inhibited proliferation of the weakly metastatic prostate cancer cell line AT-2, but was ineffective in the case of the strongly metastatic prostate cancer cell line MatLyLu [27]. On the other hand, a non-specific inhibitor of the channels, 4-amino-piridine (4-AP), significantly inhibited the proliferation of both cell lines [27].…”

Section: Kv13 Channels In Cancer Diagnostics and Therapymentioning

confidence: 99%

“…On the other hand, a non-specific inhibitor of the channels, 4-amino-piridine (4-AP), significantly inhibited the proliferation of both cell lines [27]. It was also shown that inhibition of Kv1.3 channels by a non-specific inhibitor, tetraethylamine (TEA), inhibited the proliferation of mammary epithelial M13SV1R2 and M13SV1R2-N1 cells.…”

Section: Kv13 Channels In Cancer Diagnostics and Therapymentioning

confidence: 99%

Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

Teisseyre¹,

Gąsiorowska²,

Michalak³

2015

Adv Clin Exp Med

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Voltage-gated potassium channels, Kv1.3, which were discovered in 1984, are integral membrane proteins which are activated ("open") upon change of the cell membrane potential, enabling a passive flux of potassium ions across the cell membrane. The channels are expressed in many different tissues, both normal and cancer. Since 2005 it has been known that the channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane. The activity of Kv1.3 channels plays an important role, among others, in setting the cell resting membrane potential, cell proliferation, apoptosis and volume regulation. For some years, these channels have been considered a potentially new molecular target in both the diagnostics and therapy of some cancer diseases. This review article focuses on: 1) changes of expression of the channels in cancer disorders with special regard to correlations between the channels' expression and stage of the disease, 2) influence of inhibitors of Kv1.3 channels on proliferation and apoptosis of cancer cells, 3) possible future applications of Kv1.3 channels' inhibitors in therapy of some cancer diseases. In the last section, the results of studies performed in our Laboratory of Bioelectricity on the influence of selected biologically active plant-derived compounds from the groups of flavonoids and stilbenes and their natural and synthetic derivatives on the activity of Kv1.3 channels in normal and cancer cells are reviewed. A possible application of some compounds from these groups to support therapy of cancer diseases, such as breast, colon and lymph node cancer, and melanoma or chronic lymphocytic leukemia (B-CLL), is announced (Adv Clin Exp Med 2015, 24, 3, 517-524).

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Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: Comparison of strongly and weakly metastatic cell lines

Cited by 88 publications

References 50 publications

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

Notch signalling and voltage-gated Na+ channel activity in human prostate cancer cells: independent modulation of in vitro motility

Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

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