Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 248-253

Effects of cisplatin on potassium currents in CT26 cells


1 Department of Pediatrics, School of Medicine, Research Institute of Clinical Medicine, Chonbuk National University, Jeonju, South Korea
2 Department of Oral Physiology, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeonju, South Korea

Date of Web Publication13-Apr-2016

Correspondence Address:
Seong Kyu Han
Department of Oral Physiology, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756
South Korea
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.154085

Rights and Permissions
 > Abstract 


Aims: Cisplatin, a platinum-based drug, is an important weapon against many types of cancer. It is well-known that cisplatin induces apoptosis. Potassium channel plays very important role in several signaling pathways. To investigate the possibility that potassium channels also have a role in the cellular response to cisplatin, we examined the effect of cisplatin on the activity of potassium channels on CT26 cell, the colon carcinoma cell line.
Materials and Methods: The cells were cultured in DMEM, supplemented with 10< heat-inactivated fetal bovine serum. At mid-log phase, cultures were harvested, washed twice in phosphate-buffered saline, and resuspended in culture medium before use. Cells were voltage-clamped using the whole-cell patch clamp technique. Membrane current data were collected and amplified.
Statistical Analysis: Differences between two groups were assessed by paired t-test and one sample t-test to compare the relative values. One-way ANOVA was used for all experiment with more than two groups.
Results: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.
Conclusion: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.

Keywords: CT26 colon carcinoma cells, patch-clamp, potassium currents


How to cite this article:
Sharma N, Bhattarai JP, Kim SY, Hwang PH, Kim MS, Han SK. Effects of cisplatin on potassium currents in CT26 cells. J Can Res Ther 2016;12:248-53

How to cite this URL:
Sharma N, Bhattarai JP, Kim SY, Hwang PH, Kim MS, Han SK. Effects of cisplatin on potassium currents in CT26 cells. J Can Res Ther [serial online] 2016 [cited 2019 Nov 20];12:248-53. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/248/154085




 > Introduction Top


Cancer, one of the leading causes of mortality in the world, is a devastating disease involving many steps of complex signaling pathways. Conventional treatments for cancer include surgery, chemotherapy and radiation. In addition to severe side-effects, current available treatments have low survival rate and limited clinical outcomes for many cancers. It is essential to discover new targets and therapeutic strategies to increase the survival rate and improve the clinical outcomes of cancer patients. Collective studies have shown that ion channels, the specialized membrane proteins that conduct ion fluxes, are involved in the development of many diseases, including cancers.[1] The roles of various ion channels in the growth/proliferation, migration and/or invasion of cancer cells have been well documented.[2],[3],[4],[5],[6],[7],[8]

Potassium channels conduct the flux of potassium ions through the membranes of essentially in all-living cells and generate either inward or outward currents.[9] Different subfamilies of potassium channels have been well correlated with tumor proliferation, including Ca 2+-activated potassium channels, Shaker-type, voltage-gated potassium channels, the ether à go-go family of voltage-gated potassium channels and the 2P-domain potassium channels.[10],[11],[12],[13] Voltage-gated potassium channels are widely distributed throughout excitable cells such as neurons and cardiac myocytes and control the resting membrane potential of these cells.[14],[15],[16]

In nonexcitable cells, they are involved in a number of physiological processes including volume regulation, apoptosis, immunomodulation and differentiation. In addition to physiological processes, voltage-dependent potassium channels have been shown to play a pivotal role in the proliferation, progression, and apoptosis of various cancer cells and have been considered as new targets for designing cancer treatment strategies.[17] The functional importance of potassium channels for cell cycling is further confirmed by inhibition of cell cycle initiation and progression due to application of potassium channel inhibitors. Cancer tissue were identified with different potassium channels, such as Ca 2+-activated and voltage-gated potassium channels (Kv channel), the ether à go-go family and 2P-domain potassium channels.[7] However, Kv channels seem to play an important role in tumor cells, particularly in those of epithelial origin.[6],[11],[18]

Cisplatin has been found to have toxicity in both clinical and animal studies.In vivo and In vitro experiments have shown that apoptotic cell death is the primary cause of cisplatin toxicity.[19] Furthermore, cisplatin has been reported to promote the up-regulation of the pro-apoptotic tumor suppressor gene p53, increase in bax positive and decrease in Bcl-2-positive cells and the release of cytochrome C.[20],[21],[22],[23] Although apoptosis has been directly linked to cisplatin toxicity, the effect of cisplatin on potassium current of cancerous membrane have not been well studied. Hence, in this study, we tried to figure out the functional expression of potassium channels in CT26 cells and the action of cisplatin on potassium currents in CT26 cells using whole-cell patch clamp technique.


 > Materials and Methods Top


Cell line and cell culture

The cell line CT26 and IEC-6 cell was obtained from the Korean Cell line Bank (Seoul Korea). The cells were cultured in DMEM, supplemented with10% heat-inactivated fetal bovine serum (FBS, Hyclone, Logan, UT, USA), added with 300 mg/ml glutamine, 100 units/ml penicillin G, and 100 mg/ml streptomycin sulphate (GIBCO BRL Life Technologies, Gaithersburg, MD, USA). Cultures were incubated at 37°C in the atmosphere of 5% CO2. When the cells were at mid-log phase, cultures were harvested, washed twice in phosphate-buffered saline, and resuspended in culture medium before use.

Whole-cell current recording

Cells were voltage-clamped using the whole-cell patch clamp technique. Pipettes were prepared from glass capillary (PG10165-4; WPI Inc., Sarasota, FL, USA) using the patch electrode puller (PC 10; Narishige, Tokyo, Japan). The patch pipettes had a resistance of 2.5–8 MΩ. The pipettes were positioned using a three-dimensional Vernier-type hydraulic micromanipulator (MX-630R; SOMA Scientific, Irvine, CA, USA). Seals (2–10 GΩ) were formed by applying gentle negative pressure. Voltage steps were applied to pulse protocols and ramp driven by an IBM computer equipped with A–D and D–A converters (Digidata 1200; Axon Instruments Inc., Foster City, CA, USA). Membrane current data were collected and amplified using Axopatch 200B and Clampex 7 programs (Axon Instruments Inc., Foster City, CA, USA). Data were filtered with a low-pass Bessel filter (23 dB at 1 kHz) and digitized online at a sampling frequency of 5–10 kHz for subsequent computer analysis. Data analysis was performed using Clampfit 9. All experiments were carried out at room temperature.

Solutions and drugs

To record K + current, the bath solution containing (in mM) NaCl 136, KCl 5.4, MgCl21.2, CaCl21.8, HEPES 10, Glucose 5.2 (pH = 7.4, adjusted with NaOH) was used. A pipette solution with the following composition (in mM): KCl 140, CaCl20.65, EGTA 3, HEPES 10, Glucose 10 (pH adjusted to 7.4 with KOH) was passed through a disposable 0.45 µm filter. Tetraethylammonium (TEA), apamin, iberiotoxin (IBX) and all other chemicals were purchased from Sigma (St Louis, MO, USA).

Data analysis

Data were expressed as mean ± standard error of the mean. Differences between two groups were assessed by paired t-test and one sample t-test to compare the relative values. One-way ANOVA was used for all experiment with more than two groups.


 > Results Top


Whole-cell voltage-clamp recordings were made from microscopically identified CT26 cells. The membrane potentials were held at − 40 mV. Depolarizing pulses were then applied in 20 mV steps every 3 s for 400 ms and the depolarizing pulse-induced whole-cell currents were obtained. The depolarizing pulses induced outward currents, however, no marked inward currents were observed in the same voltage ranges [Figure 1]a. The whole-cell currents remained stable for 5–10 min in the absence of intervention. These intact outward currents (772 ± 124 pA, n = 5) at the depolarizing pulse were suppressed by 2 mM barium chloride (232 ± 40.6 pA, n = 5), a broad spectrum potassium channel blocker [Figure 1]a. [Figure 1]b shows the current-voltage relationship in control, in the presence of barium chloride and washout. At the depolarizing pulse of 160 mV the relative current in presence of BaCl2 was 0.47 ± 0.14 (n = 5). These results indicate that potassium channels are functionally expressed in CT26 cells.
Figure 1: Blockage of the whole-cell outward K+ currents by BaCl2. (a) Typical examples of outward K+ currents evoked by a 400-ms depolarizing pulses from a holding potential of −40 mV in control and in the presence of 2 mM BaCl2, a potassium channel blocker. (b) Current–voltage relationship from 5 recorded cells represents mean current in control, BaCl2and washout. Values are means ± standard error of the mean *represents P < 0.05

Click here to view


Moreover to determine whether large conductance Ca 2+-activated K + (BK) channels were involved in the outward K + current, we used caffeine (3 mM) and IBX (IBX, 0.1 mM), a BK channel blocker.[24] Caffeine (3 mM), which induces Ca 2+ release from the sarcoplasmic reticulum, significantly enhanced outward potassium currents and IBX significantly decreased the outward K + currents (P < 0.05). [Figure 2]a represents outward currents induced by depolarizing pulse of 160 mV in intact, in the presence of caffeine and IBX. The current-voltage relationship in the presence of caffeine and IBX along with control is shown in [Figure 2]b. The relative currents in the presence of caffeine and in the presence of IBX were 1.7 ± 0.27 and 0.62 ± 0.15 (n = 3), respectively.
Figure 2: (a) Typical examples of outward K+ currents evoked by a 400-ms depolarizing pulse to +160 mV from a holding potential of −40 mV in control, in the presence of 3 mM caffeine and 0.1 mM iberiotoxin (IBX). (b) Current–voltage relationship recorded from cells represents mean currents in control, caffeine (n = 5) and IBX (n = 3) *represents P < 0.05

Click here to view


To check whether cisplatin can affect the potassium currents on CT26 cells, cisplatin was bath-applied. Cisplatin dramatically enhanced the depolarizing pulse-mediated outward currents on CT26 cells. [Figure 3]a shows outward currents at the depolarizing pulse of 160 mV by the application of cisplatin (0.5 mM) and cisplatin in the presence of TEA (10 mM). The mean outward current induced by depolarizing pulse of 160 mV (496.56 ± 90.46 pA, n = 10) was enhanced by 0.5 mM cisplatin application (900.35 ± 175pA, n = 10; P < 0.05 paired t- test) and partially recovered after 3 min washout (585 ± 225 pA). The relative current value in the presence of cisplatin at the depolarizing pulse of 160 mV was 1.92 ± 0.28 compared to in the absence of cisplatin. Finally to check whether the cisplatin-induced currents were mediated through the potassium channels in CT26 cells, in some cases we applied the cisplatin in the presence of TEA, cisplatin markedly increased outward currents, which were decreased by 10 mM TEA. [Figure 3]a represents outward currents induced at the depolarizing pulse of 160 mV in intact, in the presence of cisplatin and cisplatin + TEA. The current in control, in the presence of cisplatin, and cisplatin + TEA were 496 ± 90 pA 900 ± 175 pA and 268 ± 69 pA respectively. [Figure 3]b shows current-voltage relationship in the presence of cisplatin and cisplatin + TEA along with control, the threshold of activation was found to be around 80 mV. Further, to compare the effect of cisplatin on potassium currents of normal and cancer cells, cisplatin was applied on IEC-6 normal intestinal cells. The mean outward current induced by depolarizing pulse of 160 mV (722 ± 248 pA) was enhanced by 0.5 mM cisplatin application (1008 ± 340 pA, n = 7; P < 0.05, paired t-test) and subsided upon being washout (668 ± 260 pA) in IEC-6 cells. [Figure 3]c represents outward currents induced by depolarizing pulse (160 mV) in intact, in the presence of cisplatin and wash out in normal IEC-6 cells. The relative current value of cisplatin-induced current with respect to control was 1.4 ± 0.05 in IEC-6 cells [Figure 3]d. Although there was no significant difference between relative current induced by cisplatin in normal and cancer cells, it can be figured that the relative response induced by cisplatin in cancer cell was bit larger.
Figure 3: (a) Outward K+ currents evoked in control, in cisplatin (0.5 mM) and in cisplatin + tetraethylammonium (TEA) (10 mM) in CT26 cells. (b) Current–voltage relationship from 10 recorded cells represents mean currents in control, cisplatin and cisplatin + TEA. (c) Outward K+ currents in control and in cisplatin and after washout of cisplatin induced response in IEC-6 cells. (d) Bar graph shows the relative potassium current induced by cisplatin in CT26 and IEC-6 cells. Values represent means ± standard error of the mean *and NS representP < 0.05 and not significant, respectively

Click here to view



 > Discussion Top


We report here that CT26 colon cancer cells possess potassium channels, which were activated by caffeine and blocked by TEA and IBX suggesting the involvement of BK channels. We also revealed that cisplatin activates potassium currents on CT26 colon cancer cells. Importantly, we found that cisplatin-induced larger potassium currents in cancer cells than in the normal intestinal cells.

Potassium channels are most diverse family of plasma membrane channels. In epithelial cells of the gastrointestinal tract, K + channels play an important role in, absorption of nutrients and electrolytes, secretion of K +, regulation of cell volume and pH, and also in cell proliferation, differentiation, and apoptosis.[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25] Ca 2+-activated K + channels, ATP-sensitive K + channels, and 239B-sensitive KvLQT1 K + channels have been identified in small and large intestine.[13] Wonderlin and Strobl have shown that activation of K + channels is crucial for progression of the cell cycle through the G1 phase.[13] In this study, we found that the CT26 colon cancer cells possess K + currents, which get excited by caffeine and suppressed by barium and IBX [Figure 1] and [Figure 2] suggesting the involvement of BK channels. In addition, activation of large K + currents that lead to cell shrinkage in conjunction with apoptotic stimuli causes programmed cell death.[7] As an early hallmark of programmed cell death, apoptotic cells show cell shrinkage, termed apoptotic volume decrease (AVD), due to efflux of K +, Cl , and water.[7],[26] K + efflux increases two-fold in apoptosis-induced IEC-6 rat epithelial cells. K + channel inhibitors prevent DNA fragmentation, caspase activation and loss of the mitochondrial membrane potential, resulting in attenuation of apoptotic cell death. Various K + channels have been implicated in apoptosis such as Kv, BK, two-pore K + channels, hErg, ATP-sensitive K + channels and inward rectifier K + channels.[27] In our study, we found that K + channels are functionally expressed in CT26 cells.

It has also been reported that identical K + channels contribute to either proliferation or apoptosis. For instance, human Erg channels facilitate tumor cell proliferation by tumor necrosis factor alpha, and also promote H2O2-induced apoptosis in various tumors.[12],[28] In proliferative cells, activation of K + channels is necessary to maintain cell volume via regulatory volume decrease (RVD), whereas, in apoptotic cells, activation of K + channels leads to AVD cell shrinkage.[29] A previous study found a correlation between the activity of voltage-gated K + channels and proliferation and metastasis of a colonic cancer cell line and native colonic cancers, respectively.[30],[31] Interestingly Ca 2+ influx into colonic cancer cells was affected by voltage-gated K + channels in one study.[30] Identification of K + channels, which are relevant for the growth of colonic carcinomas may provide novel therapeutic targets.[32],[33] Moreover, K + channels abnormally expressed in colonic cancer cells could be potentially useful as markers for malign transformation.

Cisplatin has been a commonly employed anticancer drug for the last 40 years and continues to be among the most widely used antineoplastic drugs in clinical use.[34] Some results from both in vitro and in vivo experiments have shown that apoptotic cell death is the primary cause of cisplatin toxicity.[19]

In this study, we found that the outward currents by depolarizing pulses were enhanced by cisplatin and inhibited by TEA [Figure 3] and the outward currents were enhanced by caffeine and suppressed by IBX [Figure 2]. These results imply that cisplatin can activate the voltage-dependent K + currents and the currents were calcium sensitive. We also observed that the current induced by depolarizing pulses in normal cell line was slightly larger than that of cancer cells. This may be due to rundown of K + concentration in cancer cells.[35],[36],[37],[38] However, the relative current induced by cisplatin in cancer cells was bit larger than that of normal cells, suggesting that cisplatin-induced eflux of K + may be higher in the cancer cells. A number of studies have shown that cisplatin can affect K + currents in various tissues. For example, Liang et al. reported that cisplatin activates BK channels in the type I spiral ligament fibrocytes of the lateral wall and disrupts the electrochemical gradient thus triggering apoptosis.[39] It has also been reported that activation of BK channel induces apoptosis in estrogen-receptor-negative breast cancer cell.[40] Cisplatin-induced persistent activation of the BK channels leads to efflux of potassium ions and decrease intracellular osmotic pressure and ionic concentration which in turn triggers the pro-apoptotic nucleases, cleavage of caspases leading to cell death of lymphocytes.[41],[42]

Taken together, we found that cisplatin activates K + currents on CT26 colon cancer cells most probably through Ca 2+ activated potassium channels. This may increase the potassium efflux which may lead to apoptosis.


 > Acknowledgments Top


This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012R1A1A2003535) and (2013R1A1A2058356).

 
 > References Top

1.
Lehmann-Horn F, Jurkat-Rott K. Voltagegated ion channels and hereditary disease. Physiol Rev 1999;79:1317-72.  Back to cited text no. 1
    
2.
Le Guennec JY, Ouadid-Ahidouch H, Soriani O, Besson P, Ahidouch A, Vandier C. Voltage-gated ion channels, new targets in anti-cancer research. Recent Pat Anticancer Drug Discov 2007;2:189-202.  Back to cited text no. 2
    
3.
Fiske JL, Fomin VP, Brown ML, Duncan RL, Sikes RA. Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev 2006;25:493-500.  Back to cited text no. 3
    
4.
Roger S, Potier M, Vandier C, Besson P, Le Guennec JY. Voltage-gated sodium channels: New targets in cancer therapy? Curr Pharm Des 2006;12:3681-95.  Back to cited text no. 4
    
5.
Pardo LA, Stühmer W. Eag1: An emerging oncological target. Cancer Res 2008;68:1611-3.  Back to cited text no. 5
    
6.
Pardo LA, Contreras-Jurado C, Zientkowska M, Alves F, Stühmer W. Role of voltage-gated potassium channels in cancer. J Membr Biol 2005;205:115-24.  Back to cited text no. 6
    
7.
Kunzelmann K. Ion channels and cancer. J Membr Biol 2005;205:159-73.  Back to cited text no. 7
    
8.
Bödding M. TRP proteins and cancer. Cell Signal 2007;19:617-24.  Back to cited text no. 8
    
9.
Hille B. Ion Channels of Excitable Membranes. Sunderland, MA: Sinauer Associates; 2001.  Back to cited text no. 9
    
10.
O'Grady SM, Lee SY. Molecular diversity and function of voltage-gated (Kv) potassium channels in epithelial cells. Int J Biochem Cell Biol 2005;37:1578-94.  Back to cited text no. 10
    
11.
Pardo LA. Voltage-gated potassium channels in cell proliferation. Physiology (Bethesda) 2004;19:285-92.  Back to cited text no. 11
    
12.
Wang Z. Roles of K+channels in regulating tumour cell proliferation and apoptosis. Pflugers Arch 2004;448:274-86.  Back to cited text no. 12
    
13.
Wonderlin WF, Strobl JS. Potassium channels, proliferation and G1 progression. J Membr Biol 1996;154:91-107.  Back to cited text no. 13
    
14.
Johnston J, Forsythe ID, Kopp-Scheinpflug C. Going native: Voltage-gated potassium channels controlling neuronal excitability. J Physiol 2010;588:3187-200.  Back to cited text no. 14
    
15.
Misonou H, Trimmer JS. Determinants of voltage-gated potassium channel surface expression and localization in Mammalian neurons. Crit Rev Biochem Mol Biol 2004;39:125-45.  Back to cited text no. 15
    
16.
Tamargo J, Caballero R, Goxmez R, Valenzuela C, Delpo'n E. Pharmacology of cardiac potassium channels. Cardiovasc Res 2004;62:9-33.  Back to cited text no. 16
    
17.
Villalonga N, Ferreres JC, Argilés JM, Condom E, Felipe A. Potassium channels are a new target field in anticancer drug design. Recent Pat Anticancer Drug Discov 2007;2:212-23.  Back to cited text no. 17
    
18.
Kunzelmann K. Ion channels and cancer. J Membr Biol 2005;205:159-73.  Back to cited text no. 18
    
19.
Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. (Review). Oncol Rep 2003;10:1663-82.  Back to cited text no. 19
    
20.
Alam SA, Ikeda K, Oshima T, Suzuki M, Kawase T, Kikuchi T, et al. Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea. Hear Res 2000;141:28-38.  Back to cited text no. 20
    
21.
Devarajan P, Savoca M, Castaneda MP, Park MS, Esteban-Cruciani N, Kalinec G, et al. Cisplatin-induced apoptosis in auditory cells: Role of death receptor and mitochondrial pathways. Hear Res 2002;174:45-54.  Back to cited text no. 21
    
22.
Lee JE, Nakagawa T, Kim TS, Iguchi F, Endo T, Dong Y, et al. A novel model for rapid induction of apoptosis in spiral ganglions of mice. Laryngoscope 2003;113:994-9.  Back to cited text no. 22
    
23.
Zhang M, Liu W, Ding D, Salvi R. Pifithrin-alpha suppresses p53 and protects cochlear and vestibular hair cells from cisplatin-induced apoptosis. Neuroscience 2003;120:191-205.  Back to cited text no. 23
    
24.
Dhungel KU, Kim TW, Sharma N, Bhattarai JP, Park SA, Han SK, et al. Magnesium increases iberiotoxin-sensitive large conductance calcium activated potassium currents on the basilar artery smooth muscle cells in rabbits. Neurol Res 2012;34:11-6.  Back to cited text no. 24
    
25.
Warth R, Barhanin J. Function of K channels in the intestinal epithelium. J Membr Biol 2003;193:67-78.  Back to cited text no. 25
    
26.
Maeno E, Ishizaki Y, Kanaseki T, Hazama A, Okada Y. Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci U S A 2000;97:9487-92.  Back to cited text no. 26
    
27.
Burg ED, Remillard CV, Yuan JX. K+channels in apoptosis. J Membr Biol 2006;209:3-20.  Back to cited text no. 27
    
28.
Wang H, Zhang Y, Cao L, Han H, Wang J, Yang B, et al. HERG K+channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res 2002;62:4843-8.  Back to cited text no. 28
    
29.
Yu SP, Canzoniero LM, Choi DW. Ion homeostasis and apoptosis. Curr Opin Cell Biol 2001;13:405-11.  Back to cited text no. 29
    
30.
Abdul M, Hoosein N. Voltage-gated potassium ion channels in colon cancer. Oncol Rep 2002;9:961-4.  Back to cited text no. 30
    
31.
Lastraioli E, Guasti L, Crociani O, Polvani S, Hofmann G, Witchel H, et al. herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells. Cancer Res 2004;64:606-11.  Back to cited text no. 31
    
32.
Conti M. Targeting K+channels for cancer therapy. J Exp Ther Oncol 2004;4:161-6.  Back to cited text no. 32
    
33.
Schönherr R. Clinical relevance of ion channels for diagnosis and therapy of cancer. J Membr Biol 2005;205:175-84.  Back to cited text no. 33
    
34.
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007;7:573-84.  Back to cited text no. 34
    
35.
Cone CD Jr. Variation of the transmembrane potential level as a basic mechanism of mitosis control. Oncology 1970;24:438-70.  Back to cited text no. 35
    
36.
Cone CD Jr. The role of the surface electrical transmembrane potential in normal and malignant mitogenesis. Ann N Y Acad Sci 1974;238:420-35.  Back to cited text no. 36
    
37.
Cone CD. Transmembrane Potentials and Characteristics of Immune and Tumor Cells. Boca Raton, Florida: CRC Press; 1985.  Back to cited text no. 37
    
38.
Cope FW. A medical application of the Ling association-induction hypothesis: The high potassium, low sodium diet of the Gerson cancer therapy. Physiol Chem Phys 1978;10:465-8.  Back to cited text no. 38
    
39.
Liang F, Schulte BA, Qu C, Hu W, Shen Z. Inhibition of the calcium- and voltage-dependent big conductance potassium channel ameliorates cisplatin-induced apoptosis in spiral ligament fibrocytes of the cochlea. Neuroscience 2005;135:263-71.  Back to cited text no. 39
    
40.
Ma YG, Liu WC, Dong S, Du C, Wang XJ, Li JS, et al. Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells. PLoS One 2012;7:e37451.  Back to cited text no. 40
    
41.
Hughes FM Jr, Bortner CD, Purdy GD, Cidlowski JA. Intracellular K+suppresses the activation of apoptosis in lymphocytes. J Biol Chem 1997;272:30567-76.  Back to cited text no. 41
    
42.
Bortner CD, Cidlowski JA. A necessary role for cell shrinkage in apoptosis. Biochem Pharmacol 1998;56:1549-59.  Back to cited text no. 42
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

Top
 
 
  Search
 
Similar in PUBMED
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Materials and Me...>Results>Discussion>Acknowledgments>Article Figures
  In this article
>References

 Article Access Statistics
    Viewed2593    
    Printed53    
    Emailed0    
    PDF Downloaded138    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]