SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma
Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2024/4501154 |
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| author | Jiaxin Zhang Huiqiong Han Yihan Liu Jiayao Xu Daidi Zhang Wenjia Wang Yaping Gao Zhengrui Li Yanru Qin |
| author_facet | Jiaxin Zhang Huiqiong Han Yihan Liu Jiayao Xu Daidi Zhang Wenjia Wang Yaping Gao Zhengrui Li Yanru Qin |
| author_sort | Jiaxin Zhang |
| collection | DOAJ |
| description | Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit-8 (CCK-8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate–ribose) polymerase (PARP), caspase-9, and BCL-2 pathways in a dose-dependent and time-dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase-9, and BCL-2) and autophagy (LC3-A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth. |
| format | Article |
| id | doaj-art-d20e2cd925dd4d35b5068e073f1d1383 |
| institution | Kabale University |
| issn | 2314-4378 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-d20e2cd925dd4d35b5068e073f1d13832025-01-03T01:35:15ZengWileyInternational Journal of Genomics2314-43782024-01-01202410.1155/2024/4501154SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell CarcinomaJiaxin Zhang0Huiqiong Han1Yihan Liu2Jiayao Xu3Daidi Zhang4Wenjia Wang5Yaping Gao6Zhengrui Li7Yanru Qin8Department of OncologyDepartment of OncologyDepartment of OncologyDepartment of OncologyDepartment of OncologyDepartment of OncologyDepartment of OncologyDepartment of Oral and Maxillofacial-Head and Neck OncologyDepartment of OncologyCalcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit-8 (CCK-8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate–ribose) polymerase (PARP), caspase-9, and BCL-2 pathways in a dose-dependent and time-dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase-9, and BCL-2) and autophagy (LC3-A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth.http://dx.doi.org/10.1155/2024/4501154 |
| spellingShingle | Jiaxin Zhang Huiqiong Han Yihan Liu Jiayao Xu Daidi Zhang Wenjia Wang Yaping Gao Zhengrui Li Yanru Qin SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma International Journal of Genomics |
| title | SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma |
| title_full | SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma |
| title_fullStr | SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma |
| title_full_unstemmed | SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma |
| title_short | SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma |
| title_sort | skf96365 inhibits tumor proliferation by inducing apoptosis and autophagy in human esophageal squamous cell carcinoma |
| url | http://dx.doi.org/10.1155/2024/4501154 |
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