Tamoxifen Inhibition of Kv7.2/Kv7.3 Channels

Ferrer, Tania; Aréchiga-Figueroa, Iván A.; Shapiro, Mark S.; Tristani‐Firouzi, Martin; Sánchez-Chapula, José A.

doi:10.1371/journal.pone.0076085

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…Tamoxifen induced apoptosis and exerted cytotoxic effects in rat glioma cell, in a concentration and dose dependant manner [ 115 ]. Due to its inhibitory effects on PIP2 sensitive channels, it is suggested that that tamoxifen inhibits the Kv7.2/Kv7.3 by obstructing PIP2-channel interaction, however the exact mechanism by which tamoxifen inhibits K+ channels in unknown [ 153 ].…”

Section: Ion Channel Inhibitors As Therapeutic Targetsmentioning

confidence: 99%

Ion Channels as Therapeutic Targets in High Grade Gliomas

Griffin

Khan

Basu

et al. 2020

Cancers

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Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

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Section: Ion Channel Inhibitors As Therapeutic Targetsmentioning

confidence: 99%

Ion Channels as Therapeutic Targets in High Grade Gliomas

Griffin

Khan

Basu

et al. 2020

Cancers

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“…KCNQ genes encode five Kv7 channel subunits, named Kv7.1-Kv7.5. While the Kv7.1 isoform can be found in different cell lineages, including cardiac myocytes and epithelial cells [29], Kv7.2-Kv7.5 are mainly found in the nervous system, as Kv7.2 and Kv7.3 are the main molecular components of the slow voltage-gated M-channel responsible for fine-tuning neuronal excitability [30]. In respect to the already characterized modulators of this voltage-gated potassium channel family, only a few examples of animal-derived components are currently known.…”

Section: Discussionmentioning

confidence: 99%

A Tale of Toxin Promiscuity: The Versatile Pharmacological Effects of Hcr 1b-2 Sea Anemone Peptide on Voltage-Gated Ion Channels

et al. 2022

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Sea anemones are a rich source of biologically active compounds. Among approximately 1100 species described so far, Heteractis crispa species, also known as sebae anemone, is native to the Indo-Pacific area. As part of its venom components, the Hcr 1b-2 peptide was first described as an ASIC1a and ASIC3 inhibitor. Using Xenopus laevis oocytes and the two-electrode voltage-clamp technique, in the present work we describe the remarkable lack of selectivity of this toxin. Besides the acid-sensing ion channels previously described, we identified 26 new targets of this peptide, comprising 14 voltage-gated potassium channels, 9 voltage-gated sodium channels, and 3 voltage-gated calcium channels. Among them, Hcr 1b-2 is the first sea anemone peptide described to interact with isoforms from the Kv7 family and T-type Cav channels. Taken together, the diversity of Hcr 1b-2 targets turns this toxin into an interesting tool to study different types of ion channels, as well as a prototype to develop new and more specific ion channel ligands.

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“…However, canine osteosarcoma cell proliferation decreases the expression of Kv7.5 [ 19 ]. Furthermore, tamoxifen, which efficiently inhibits Kv7.2/Kv7.3 activity, is used in breast cancer therapy [ 27 ]. All this evidence suggests that Kv7 channels are remodeled by cancer, mostly through increasing their expression.…”

Section: Discussionmentioning

confidence: 99%

Remodeling of Kv7.1 and Kv7.5 Expression in Vascular Tumors

Serrano-Novillo

Oliveras

Ferreres

et al. 2020

IJMS

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Voltage-dependent potassium (Kv) channels contribute to the excitability of nerves and muscles. In addition, Kv participates in several cell functions, including cell cycle progression and proliferation. Kv channel remodeling has been associated with neoplastic cell growth and cancer. Kv7 channels are expressed in blood vessels, and they participate in the maintenance of vascular tone and are implicated in myocyte proliferation. Although evidence links Kv7 remodeling to different types of cancer, its expression in vascular tumors has never been studied. Endothelium-derived vascular neoplasms range from indolent lesions to highly aggressive and metastasizing cancers. Here, we show that Kv7.1 and Kv7.5 are evenly distributed in tunicas as well as the endothelium of healthy veins and arteries. The layered structure of vessels is lost in vascular tumors. By studying eight vascular tumors with different origins and characteristics, we found that Kv7.1 and Kv7.5 expression was changed in vascular cancers. While both channels were generally downregulated, Kv7.5 expression was clearly correlated with neoplastic malignancy. The vascular tumors did not contract; therefore, the role of Kv7 channels is probably related to proliferation rather than controlling vascular tone. Our results identify vascular Kv7 channels as targets for cancer detection and anticancer therapies.

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Tamoxifen Inhibition of Kv7.2/Kv7.3 Channels

Cited by 7 publications

References 37 publications

Ion Channels as Therapeutic Targets in High Grade Gliomas

Ion Channels as Therapeutic Targets in High Grade Gliomas

A Tale of Toxin Promiscuity: The Versatile Pharmacological Effects of Hcr 1b-2 Sea Anemone Peptide on Voltage-Gated Ion Channels

Remodeling of Kv7.1 and Kv7.5 Expression in Vascular Tumors

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