Ion Transport and Radioresistance

Roth, Bastian; Huber, Stephan M.

doi:10.1007/112_2020_33

Cited by 6 publications

(4 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CamKII inhibits cdc25 phosphatase, which prevents the activation of phosphorylated cdc2. Instead, the cyclin B-cdc2 complex, when activated, arrests the cell cycle in G2/M [127]. As TRAM-34 had a negligible effect on the cell cycle of unirradiated T98G cells, the above results are in agreement with Abdullaev et al (2010).…”

Section: Kca31 Inhibitors Affect Proliferative Capacity On Irradiated...supporting

confidence: 70%

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Calderón,

Arvelo

2024

Cell Physiol Biochem

View full text Add to dashboard Cite

Anomalous expression of potassium channels in cancer tissues is associated with several cancer hallmarks that support deregulated proliferation and tumor progression. Ion channels seem to influence cell proliferation; however, the crucial molecular mechanisms involved remain elusive. Some results show how extracellular mitogenic signals modulate ion channel activity through intracellular secondary messengers. It is relevant because we are beginning to understand how potassium channels can affect the proliferative capacity of cells, either in normal mitogen-dependent proliferation or in mitogen-unresponsive proliferation. Calcium- dependent potassium channels have been implicated in cell cycle signaling in many cancerous cell lines. In particular, the so-called intermediate conductance KCa3.1 (IKCa) is reported to play a significant role in uncontrolled cell cycle signaling, among other malignant processes driven by cancer hallmarks. In addition to these features, this channel can be subjected to specific pharmacological regulation, making it a promising cornerstone for understanding the signaling behavior of several types of cancer and as a target for chemotherapeutic approaches. This review is dedicated to the connection of KCa3.1 activity, in canonical and non-canonical ways, to the cell cycle signaling, including the cooperation with calcium channels to generate calcium signals and its role as a mediator of proliferative signals.

show abstract

Section: Kca31 Inhibitors Affect Proliferative Capacity On Irradiated...supporting

confidence: 70%

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Calderón,

Arvelo

2024

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Along those lines, in our previous work, TTFields-induced activation of L-type voltage-gated Ca v 1.2 Ca 2+ channels in one human glioblastoma cell line exerted rather pro-survival (Neuhaus et al, 2019) than tumoricidal effects (Figure 5). Therefore, a better understanding of the functional significance of potential electrobiological transducer channels in tumor biology and therapy resistance (for reviews see Huber, 2013;Klumpp et al, 2016;Roth and Huber, 2022) is inevitable for the development of further strategies in cancer electrotherapy. Such future strategies might aim to augment electrotherapy-induced cellular stress or to suppress cellular resistance mechanisms by concomitant targeting of potential resistance-mediating transducer channels.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, glioblastoma, a primary brain tumor with poor patient prognosis, over-expresses TRPM8 (member 8 of the melastatin sub-family of transient receptor potential) unselective cation channels, intermediate conductance IK Ca (KCNN4) and high conductance BK Ca (KCNMA1) K + channels. These channels reportedly contribute to glioblastoma stem cell properties, program and execute cell migration and brain invasion, regulate cell cycle, or confer therapy resistance (for review see Huber, 2013;Roth and Huber, 2022). Unexpectedly, ionizing radiation in a clinical relevant dose may induce hypermigration of human glioblastoma cells in vitro (Steinle et al, 2011) and brain invasion in an orthotopic glioma xenograft mouse model (Edalat et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Ion channels as molecular targets of glioblastoma electrotherapy

Abed

Ganser

Eckert

et al. 2023

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

Therapies with weak, non-ionizing electromagnetic fields comprise FDA-approved treatments such as Tumor Treating Fields (TTFields) that are used for adjuvant therapy of glioblastoma. In vitro data and animal models suggest a variety of biological TTFields effects. In particular, effects ranging from direct tumoricidal, radio- or chemotherapy-sensitizing, metastatic spread-inhibiting, up to immunostimulation have been described. Diverse underlying molecular mechanisms, such as dielectrophoresis of cellular compounds during cytokinesis, disturbing the formation of the spindle apparatus during mitosis, and perforating the plasma membrane have been proposed. Little attention, however, has been paid to molecular structures that are predestinated to percept electromagnetic fields—the voltage sensors of voltage-gated ion channels. The present review article briefly summarizes the mode of action of voltage sensing by ion channels. Moreover, it introduces into the perception of ultra-weak electric fields by specific organs of fishes with voltage-gated ion channels as key functional units therein. Finally, this article provides an overview of the published data on modulation of ion channel function by diverse external electromagnetic field protocols. Combined, these data strongly point to a function of voltage-gated ion channels as transducers between electricity and biology and, hence, to voltage-gated ion channels as primary targets of electrotherapy.

show abstract

“…There is evidence for the involvement of a range of ion channels and MIMs in response to radiation, especially as regards induced tumor cell death [ 52 ]. Ionic mechanisms also play a significant role in resistance to radiotherapy [ 53 ].…”

Section: Therapeutic Modalitiesmentioning

confidence: 99%

Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms

Djamgoz

2022

Cancers

View full text Add to dashboard Cite

Cancer is a global health problem that 1 in 2–3 people can expect to experience during their lifetime. Several different modalities exist for cancer management, but all of these suffer from significant shortcomings in both diagnosis and therapy. Apart from developing completely new therapies, a viable way forward is to improve the efficacy of the existing modalities. One way is to combine these with each other or with other complementary approaches. An emerging latter approach is derived from ionic mechanisms, mainly ion channels and exchangers. We evaluate the evidence for this systematically for the main treatment methods: surgery, chemotherapy, radiotherapy and targeted therapies (including monoclonal antibodies, steroid hormones, tyrosine kinase inhibitors and immunotherapy). In surgery, the possible systemic use of local anesthetics to suppress subsequent relapse is still being discussed. For all the other methods, there is significant positive evidence for several cancers and a range of modulators of ionic mechanisms. This applies also to some of the undesirable side effects of the treatments. In chemotherapy, for example, there is evidence for co-treatment with modulators of the potassium channel (Kv11.1), pH regulation (sodium–hydrogen exchanger) and Na+-K+-ATPase (digoxin). Voltage-gated sodium channels, shown previously to promote metastasis, appear to be particularly useful for co-targeting with inhibitors of tyrosine kinases, especially epidermal growth factor. It is concluded that combining current orthodox treatment modalities with modulators of ionic mechanisms can produce beneficial effects including (i) making the treatment more effective, e.g., by lowering doses; (ii) avoiding the onset of resistance to therapy; (iii) reducing undesirable side effects. However, in many cases, prospective clinical trials are needed to put the findings firmly into clinical context.

show abstract

Ion Transport and Radioresistance

Cited by 6 publications

References 173 publications

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Ion channels as molecular targets of glioblastoma electrotherapy

Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms

Contact Info

Product

Resources

About