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
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 29...
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2023-03-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2023-0010 |
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| author | Xiong Weichen Fan Huizhen Zeng Qingye Deng Zhenhui Li Guanhui Lu Wancheng Zhang Bei Lai Shian Chen Xin Xu Xueqing |
| author_facet | Xiong Weichen Fan Huizhen Zeng Qingye Deng Zhenhui Li Guanhui Lu Wancheng Zhang Bei Lai Shian Chen Xin Xu Xueqing |
| author_sort | Xiong Weichen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3d1e6d60a17d4308b6748f3fc35fd40a |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2023-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-3d1e6d60a17d4308b6748f3fc35fd40a2025-02-02T14:50:11ZengSciendoActa Pharmaceutica1846-95582023-03-0173114515510.2478/acph-2023-0010The in vitro anticancer effects of FS48 from salivary glands of Xenopsylla cheopis on NCI-H460 cells via its blockage of voltage-gated K+ channelsXiong Weichen0Fan Huizhen1Zeng Qingye2Deng Zhenhui3Li Guanhui4Lu Wancheng5Zhang Bei6Lai Shian7Chen Xin8Xu Xueqing9Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital Southern Medical University, Guangzhou510282, ChinaDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital Southern Medical University, Guangzhou510282, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, ChinaDepartment of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University Kyotanabe, Kyoto610-0394, JapanDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital Southern Medical University, Guangzhou510282, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou510515, ChinaVoltage-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.https://doi.org/10.2478/acph-2023-0010lung cancerkv channelsfs48nci-h460 cellsanticancer |
| spellingShingle | Xiong Weichen Fan Huizhen Zeng Qingye Deng Zhenhui Li Guanhui Lu Wancheng Zhang Bei Lai Shian Chen Xin Xu Xueqing 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 Acta Pharmaceutica lung cancer kv channels fs48 nci-h460 cells anticancer |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | in vitro anticancer effects of fs48 from salivary glands of xenopsylla cheopis on nci h460 cells via its blockage of voltage gated k channels |
| topic | lung cancer kv channels fs48 nci-h460 cells anticancer |
| url | https://doi.org/10.2478/acph-2023-0010 |
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