<abstract xmlns="http://www.w3.org/1999/xhtml">

Voltage-gated K+ (Kv) channels play a role in the cellular processes of various cancer cells, including lung cancer cells. We previously identified and reported a salivary protein from the <italic>Xenopsylla cheopis</italic>, FS48, which exhibited inhibitory activity against Kv1.1-1.3 channels when assayed in HEK 293T cells. However, whether FS48 has an inhibitory effect on cancer cells expressing Kv channels is unclear. The present study aims to reveal the effects of FS48 on the Kv channels and the NCI-H460 human lung cancer cells through patch clamp, MTT, wound healing, transwell, gelatinase zymography, qRT-PCR and WB assays. The results demonstrated that FS48 can be effective in suppressing the Kv currents, migration, and invasion of NCI-H460 cells in a dose-dependent manner, despite the failure to inhibit the proliferation. Moreover, the expression of Kv1.1 and Kv1.3 mRNA and protein were found to be significantly reduced. Finally, FS48 decreases the mRNA level of MMP-9 while increasing TIMP-1 mRNA level. The present study highlights for the first time that blood-sucking arthropod saliva-derived protein can inhibit the physiological activities of tumour cells <italic>via</italic> the Kv channels. Furthermore, FS48 can be taken as a hit compound against the tumour cells expressing Kv channels.
</abstract>

Voltage-gated K+ (Kv) channels play a role in the cellular processes of various cancer cells, including lung cancer cells. We previously identified and reported a salivary protein from the Xenopsylla cheopis, FS48, which exhibited inhibitory activity against Kv1.1-1.3 channels when assayed in HEK 293T cells. However, whether FS48 has an inhibitory effect on cancer cells expressing Kv channels is unclear. The present study aims to reveal the effects of FS48 on the Kv channels and the NCI-H460 human lung cancer cells through patch clamp, MTT, wound healing, transwell, gelatinase zymography, qRT-PCR and WB assays. The results demonstrated that FS48 can be effective in suppressing the Kv currents, migration, and invasion of NCI-H460 cells in a dose-dependent manner, despite the failure to inhibit the proliferation. Moreover, the expression of Kv1.1 and Kv1.3 mRNA and protein were found to be significantly reduced. Finally, FS48 decreases the mRNA level of MMP-9 while increasing TIMP-1 mRNA level. The present study highlights for the first time that blood-sucking arthropod saliva-derived protein can inhibit the physiological activities of tumour cells via the Kv channels. Furthermore, FS48 can be taken as a hit compound against the tumour cells expressing Kv channels.

The <italic>in vitro</italic> anticancer effects of FS48 from salivary glands of <italic>Xenopsylla cheopis</italic> on NCI-H460 cells <italic>via</italic> its blockage of voltage-gated K+ channels

Department of Pulmonary and Critical Care Medicine

Zhujiang Hospital Southern Medical University

Guangdong Provincial Key Laboratory of New Drug Screening

School of Pharmaceutical Sciences, Southern Medical University

Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The  anticancer effects of FS48 from salivary glands of  on NCI-H460 cells  its blockage of voltage-gated K channels

Voltage-gated K+ (Kv) channels play a role in the cellular processes of various cancer cells, including lung cancer cells. We previously identified and...

The in vitro anticancer effects of FS48 from salivary glands of Xenopsylla cheopis on NCI-H460 cells via its blockage of voltage-gated K⁺ channels

Published Online: Jan 24, 2023

Page range: 145 - 155

Accepted: Aug 23, 2022

DOI: https://doi.org/10.2478/acph-2023-0010

Keywords
lung cancer, K channels, FS48, NCI-H460 cells, anticancer

© 2023 Weichen Xiong et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The in vitro anticancer effects of FS48 from salivary glands of Xenopsylla cheopis on NCI-H460 cells via its blockage of voltage-gated K+ channels

Published Online: Jan 24, 2023

Page range: 145 - 155

Accepted: Aug 23, 2022

DOI: https://doi.org/10.2478/acph-2023-0010

Keywordslung cancer, K channels, FS48, NCI-H460 cells, anticancer

© 2023 Weichen Xiong et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The in vitro anticancer effects of FS48 from salivary glands of Xenopsylla cheopis on NCI-H460 cells via its blockage of voltage-gated K⁺ channels

Keywords
lung cancer, K channels, FS48, NCI-H460 cells, anticancer