Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

Rajaratinam, Harishini; Mokhtar, Najat; Nurul, Asma Abdullah; Fuad, Wan Ezumi Mohd

doi:10.3390/biom12020310

Cited by 3 publications

(1 citation statement)

References 176 publications

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“…VGSCs are present in excitable and non-excitable cells, including microglia, astrocytes, immune cells, fibroblasts, and cancer cells, and play various biological roles, such as tumour cell migration and immune cell phagocytosis ( Black and Waxman, 2013 ; Roger et al, 2015 ). Nav1.5, encoded by SCN5A, is an essential receptor in breast cancer growth and migration ( Rajaratinam et al, 2022 ). Notably, inhibition of Nav1.5 function or expression can inhibit breast cancer cell migration in vivo and in vitro ( Brackenbury et al, 2007 ; Nelson et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Yin

Feng

et al. 2023

Front. Pharmacol.

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Nav1.5 channel is crucial for the proliferation and migration of breast cancer cells. In this study, we investigated the anticancer effect of JZTX-14, a natural peptide considered an effective antagonist of Nav1.5. First, we successfully isolated and purified the 31 amino acid peptide JZTX-14 containing three pairs of disulfide bonds from spider venom and synthesised JZTX-14 by solid phase synthesis. We then predicted their physiochemical properties and structures in the peptide database. Further, we investigated the effects of natural and synthetic JZTX-14 on the proliferation and migration of MDA-MB-231 breast cancer cells via modulation of sodium current through the Nav1.5 channel. The results showed that both synthetic and natural JZTX-14 inhibited Nav1.5 currents, indicating the successful synthesis of JZTX-14. However, JZTX-14 did not affect MDA-MB-231 cell proliferation but inhibited its migration. Transcriptome analysis revealed that JZTX-14 downregulated S100A4 and FBXO2 and upregulated SERPINB2 in MDA-MB-231 cells. Western blot analysis demonstrated an increased level of the epithelial marker, E-cadherin, and decreased levels of the mesenchymal markers, N-cadherin and vimentin, and matrix metalloproteinase (MMP2), indicating the possible underlying mechanism of the inhibition of MDA-MB-231 cell migration by JZTX-14. This study provides a new target for inhibiting breast cancer metastasis and identifies a potent natural peptide for treating Triple-negative breast cancer.

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Section: Introductionmentioning

confidence: 99%

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Yin

Feng

et al. 2023

Front. Pharmacol.

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Voltage-gated sodium channels in cancers

Liu,

Weng,

Huang

et al. 2024

Biomark Res

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Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from “non-excitable” tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers. Here, we review the expression patterns of all nine VGSC α-subunit genes (SCN1A-11A) and their four regulatory β-subunit genes (SCN1B-4B). We reviewed data from the Cancer Genome Atlas (TCGA) database, complemented by an extensive search of the published papers. We summarized and reviewed previous independent studies and analyzed the VGSC genes in the TCGA database regarding the potential impact of VGSC on cancers. A comparison between evidence gathered from independent studies and data review was performed to scrutinize potential biases in prior research and provide insights into future research directions. The review supports the view that VGSCs play an important role in diagnostics as well as therapeutics of some cancer types, such as breast, colon, prostate, and lung cancer. This paper provides an overview of the current knowledge on voltage-gated sodium channels in cancer, as well as potential avenues for further research. While further research is required to fully understand the role of VGSCs in cancer, the potential of VGSCs for clinical diagnosis and treatment is promising.

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Evaluation of the effectiveness of detoxification in the immunorehabilitation of cancer patients

Savchenko,

Kasparov,

Borisov

et al. 2023

Cytokines and inflammation

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Purpose. Evaluation of the effectiveness of detoxification using enterosorbents in the immunorehabilitation of cancer patients. Materials and methods. 87 patients with metastatic forms of solid tumors of various localizations with metastatic lesions were examined. The patients were divided into 2 groups: study group (41 patients who received detoxification therapy in addition to standard therapy) and comparison group (46 patients who received only standard therapy). The effectiveness of therapy with these drugs was evaluated after one month by assessing clinical and immunological parameters. The assessment of the state of cellular immunity was carried out by flow cytometry. Results. Disturbances in the function of the immune system in the form of insufficiency of the cellular effector link of immunity were detected in all examined patients before the start of therapy. The state of the cellular link of immunity was characterized by an increase in the number of transitional and non-classical subsets of monocytes, an increase in the content of T-, B- and NKT-cells, but with a decrease in NK-cells. An increase in the ratio between the number of T-helpers (CD3+CD4+) and the number of cytotoxic T-cells (CD3+CD8+) was observed in the examined patients. Restoration of cell subsets to the level of control values was found in the examined patients after detoxification therapy as part of immunorehabilitation measures. Significant changes in the number of cells in the blood were absent in the comparison group after the therapy which indicated the absence of a complete relief of the systemic inflammatory response. Conclusion. Chronic toxicosis with the development of a systemic inflammatory reaction on the background of the immune system dysfunctions were found in cancer patients. The use of enterosorbents in complex immunorehabilitation therapy is substantiated and confirmed by the relief of asthenovegetative and dyspeptic syndromes, normalization of the immune system which makes it possible to recommend detoxification therapy during immunorehabilitation measures.

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Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

Cited by 3 publications

References 176 publications

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Voltage-gated sodium channels in cancers

Evaluation of the effectiveness of detoxification in the immunorehabilitation of cancer patients

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