T-type Ca2+ channel blockers suppress the growth of human cancer cells

Heo, Jae Ho; Seo, Han Na; Choe, Yong Kyung; Kim, Sujin; Oh, Chun Rim; Kim, Young Deuk; Rhim, Hyewhon; Choo, Dong Joon; Kim, Jungahn; Lee, Jae Yeol

doi:10.1016/j.bmcl.2008.06.034

Cited by 56 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various hepatocarcinoma cell lines have been found to express one or more alpha-1, T-type Ca 2+ channel subunits, although obvious T-type currents have been detected only in one of these cell types [68]. According to the supposed role of T-type channels in tumour cell growth, the possible anti-cancer use of T-type channel blockers has been investigated [69]. …”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H₂O₂−dependent T‐type Ca²⁺ channel opening

Ranzato

Martinotti

Magnelli

et al. 2012

J Cellular Molecular Medi

View full text Add to dashboard Cite

Malignant mesothelioma (MMe) is a highly aggressive, lethal tumour requiring the development of more effective therapies. The green tea polyphenol epigallocathechin-3-gallate (EGCG) inhibits the growth of many types of cancer cells. We found that EGCG is selectively cytotoxic to MMe cells with respect to normal mesothelial cells. MMe cell viability was inhibited by predominant induction of apoptosis at lower doses and necrosis at higher doses. EGCG elicited H2O2 release in cell cultures, and exogenous catalase (CAT) abrogated EGCG-induced cytotoxicity, apoptosis and necrosis. Confocal imaging of fluo 3-loaded, EGCG-exposed MMe cells showed significant [Ca2+]i rise, prevented by CAT, dithiothreitol or the T-type Ca2+ channel blockers mibefradil and NiCl2. Cell loading with dihydrorhodamine 123 revealed EGCG-induced ROS production, prevented by CAT, mibefradil or the Ca2+ chelator BAPTA-AM. Direct exposure of cells to H2O2 produced similar effects on Ca2+ and ROS, and these effects were prevented by the same inhibitors. Sensitivity of REN cells to EGCG was correlated with higher expression of Cav3.2 T-type Ca2+ channels in these cells, compared to normal mesothelium. Also, Cav3.2 siRNA on MMe cells reduced in vitro EGCG cytotoxicity and abated apoptosis and necrosis. Intriguingly, Cav3.2 expression was observed in malignant pleural mesothelioma biopsies from patients, but not in normal pleura. In conclusion, data showed the expression of T-type Ca2+ channels in MMe tissue and their role in EGCG selective cytotoxicity to MMe cells, suggesting the possible use of these channels as a novel MMe pharmacological target.

show abstract

Section: Discussionmentioning

confidence: 99%

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H₂O₂−dependent T‐type Ca²⁺ channel opening

Ranzato

Martinotti

Magnelli

et al. 2012

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…In contrast, the pharmacological blockade of Ca v 3.2 T-type Ca 2+ channels might be suitable for the treatment of prostate cancer. Actually, several blockers of T-type Ca 2+ channel appear to inhibit the proliferation and migration of androgen-independent prostate cancer DU-145 cells [66] . Although there is no report concerning the development of selective blockers of Ca v 3.2 channels, ascorbic acid (vitamin C) and zinc block Ca v 3.2, but not Ca v 3.1 or Ca v 3.3 [23,24] .…”

Section: The H 2 S/ca V 32 Pathway Regulates Neuroendocrine Secretiomentioning

confidence: 99%

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

View full text Add to dashboard Cite

Background: Hydrogen sulfide (H₂S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H₂S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Ca_v3.2 T-type Ca²⁺ channels mediate some of the biological activity of H₂S, we focus on the role of the H₂S/Ca_v3.2 pathway in regulating the neuronal and neuroendocrine function. Summary: In the neuronal system, H₂S regulates the activity of various ion channels including Ca_v3.2. Exogenous and endogenous H₂S enhances the Ca_v3.2 channel activity, promoting somatic and visceral pain signaling. The H₂S/Ca_v3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H₂S formed by CSE regulates secretory function by enhancing Ca_v3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H₂S/Ca_v3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.

show abstract

“…This pathway has the potential for targeting in future strategies for the treatment of vascular diseases. There are also important implications arising from our studies for other diseases including various cancers where Ttype Ca 2+ channels have been shown to regulate proliferation (Panner and Wurster 2006;Heo et al 2008).…”

Section: Xx5 Discussionmentioning

confidence: 96%

T-Type Ca2+ Channel Regulation by CO: A Mechanism for Control of Cell Proliferation

Duckles

Al‐Owais

Elíes

et al. 2015

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Abstract. T-type Ca2+ channels regulate proliferation in a number of tissue types, including vascular smooth muscle and various cancers. In such tissues, up-regulation of the inducible enzyme heme oxygenase-1 (HO-1) is often observed. HO-1 degrades heme to generate carbon monoxide (CO) along with Fe 2+ and biliverdin. Since CO is increasingly recognized as a regulator of ion channels, we have explored the possibility that it may regulate proliferation via modulation of T-type Ca 2+ channels. Whole-cell patch-clamp recordings revealed that CO (applied as the dissolved gas or via CORM donors) inhibited all 3 isoforms of T-type Ca 2+ channels (Cav3.1-3.3) when expressed in HEK293 cells with similar IC50 values, and induction of HO-1 expression also suppressed T-type currents. CO / HO-1 induction also suppressed the elevated basal [Ca 2+ ]i in cells expressing these channels and reduced their proliferative rate to levels seen in non-transfected control cells. Proliferation of vascular smooth muscle cells (both A7r5 and human saphenous vein cells) was also suppressed either by T-type Ca 2+ channel inhibitors (mibefradil and NNC 55-0396), HO-1 induction or application of CO. Effects of these blockers and CO were non additive. Although L-type Ca 2+ channels were also sensitive to CO, they did not influence proliferation. Our data suggest that HO-1 acts to control proliferation via CO modulation of T-type Ca 2+ channels.

show abstract

T-type Ca2+ channel blockers suppress the growth of human cancer cells

Cited by 56 publications

References 23 publications

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H₂O₂−dependent T‐type Ca²⁺ channel opening

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H₂O₂−dependent T‐type Ca²⁺ channel opening

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

T-Type Ca2+ Channel Regulation by CO: A Mechanism for Control of Cell Proliferation

Contact Info

Product

Resources

About

T-type Ca2+ channel blockers suppress the growth of human cancer cells

Cited by 56 publications

References 23 publications

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H2O2−dependent T‐type Ca2+ channel opening

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H2O2−dependent T‐type Ca2+ channel opening

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

T-Type Ca2+ Channel Regulation by CO: A Mechanism for Control of Cell Proliferation

Contact Info

Product

Resources

About

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H₂O₂−dependent T‐type Ca²⁺ channel opening

Epigallocatechin‐3‐gallate induces mesothelioma cell death via H₂O₂−dependent T‐type Ca²⁺ channel opening