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

Wenfang Wu; Wenfang Wu; Yuan Yin; Yuan Yin; Peihao Feng; Gong Chen; Gong Chen; Liangyu Pan; Liangyu Pan; Panyang Gu; Panyang Gu; Siqin Zhou; Siqin Zhou; Fulong Lin; Fulong Lin; Siyu Ji; Siyu Ji; Chunbing Zheng; Meichun Deng; Meichun Deng

doi:10.3389/fphar.2023.1067665

Frontiers in Pharmacology (Mar 2023)

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

Wenfang Wu,
Wenfang Wu,
Yuan Yin,
Yuan Yin,
Peihao Feng,
Gong Chen,
Gong Chen,
Liangyu Pan,
Liangyu Pan,
Panyang Gu,
Panyang Gu,
Siqin Zhou,
Siqin Zhou,
Fulong Lin,
Fulong Lin,
Siyu Ji,
Siyu Ji,
Chunbing Zheng,
Meichun Deng,
Meichun Deng

Affiliations

Wenfang Wu: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Wenfang Wu: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Yuan Yin: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Yuan Yin: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Peihao Feng: Xiangya School of Medicine, Central South University, Changsha, Hunan, China
Gong Chen: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Gong Chen: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Liangyu Pan: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Liangyu Pan: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Panyang Gu: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Panyang Gu: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Siqin Zhou: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Siqin Zhou: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Fulong Lin: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Fulong Lin: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Siyu Ji: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Siyu Ji: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Chunbing Zheng: Hunan Yuanpin Cell Technology Co. Ltd, Hunan, China
Meichun Deng: Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, China
Meichun Deng: Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China

DOI: https://doi.org/10.3389/fphar.2023.1067665
Journal volume & issue: Vol. 14

Abstract

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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.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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