Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway
Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect...
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MDPI AG
2020-01-01
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| Online Access: | https://www.mdpi.com/1420-3049/25/2/326 |
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| author | Min-Hong Hsieh Jia-Sin Yang Renn-Chia Lin Yi-Hsien Hsieh Shun-Fa Yang Horng-Rong Chang Ko-Hsiu Lu |
| author_facet | Min-Hong Hsieh Jia-Sin Yang Renn-Chia Lin Yi-Hsien Hsieh Shun-Fa Yang Horng-Rong Chang Ko-Hsiu Lu |
| author_sort | Min-Hong Hsieh |
| collection | DOAJ |
| description | Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway. Tomatidine, up to 100 μM, without cytotoxicity, inhibited the invasion and migration capabilities of human osteosarcoma U2OS and HOS cells and repressed presenilin 1 (PS-1) expression of U2OS cells. After the knockdown of PS-1, U2OS and HOS cells’ biological behaviors of cellular invasion and migratory potential were significantly reduced. While tomatidine significantly decreased the phosphorylation of c-Raf, mitogen/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated protein kinase (ERK)1/2 in U2OS cells, no obvious influences on p-Jun N-terminal kinase, p38, and Akt, including their phosphorylation, were observed. In ERK 1 silencing U2 OS cells, tomatidine further enhanced the decrease of their migratory potential and invasive activities. We conclude that both PS-1 derived from U2OS and HOS cells and the c-Raf−MEK−ERK pathway contribute to cellular invasion and migration and tomatidine could inhibit the phenomenons. These findings indicate that tomatidine might be a potential candidate for anti-metastasis treatment of human osteosarcoma. |
| first_indexed | 2024-12-11T09:01:16Z |
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| language | English |
| last_indexed | 2024-12-11T09:01:16Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bec631fc1e7a495ba2fbb553a4659f112022-12-22T01:13:45ZengMDPI AGMolecules1420-30492020-01-0125232610.3390/molecules25020326molecules25020326Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK PathwayMin-Hong Hsieh0Jia-Sin Yang1Renn-Chia Lin2Yi-Hsien Hsieh3Shun-Fa Yang4Horng-Rong Chang5Ko-Hsiu Lu6Institute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanDepartment of Orthopedics, Chung Shan Medical University Hospital, Taichung 402, TaiwanInstitute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanDepartment of Orthopedics, Chung Shan Medical University Hospital, Taichung 402, TaiwanOsteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway. Tomatidine, up to 100 μM, without cytotoxicity, inhibited the invasion and migration capabilities of human osteosarcoma U2OS and HOS cells and repressed presenilin 1 (PS-1) expression of U2OS cells. After the knockdown of PS-1, U2OS and HOS cells’ biological behaviors of cellular invasion and migratory potential were significantly reduced. While tomatidine significantly decreased the phosphorylation of c-Raf, mitogen/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated protein kinase (ERK)1/2 in U2OS cells, no obvious influences on p-Jun N-terminal kinase, p38, and Akt, including their phosphorylation, were observed. In ERK 1 silencing U2 OS cells, tomatidine further enhanced the decrease of their migratory potential and invasive activities. We conclude that both PS-1 derived from U2OS and HOS cells and the c-Raf−MEK−ERK pathway contribute to cellular invasion and migration and tomatidine could inhibit the phenomenons. These findings indicate that tomatidine might be a potential candidate for anti-metastasis treatment of human osteosarcoma.https://www.mdpi.com/1420-3049/25/2/326erkmetastasisosteosarcomaps-1tomatidine |
| spellingShingle | Min-Hong Hsieh Jia-Sin Yang Renn-Chia Lin Yi-Hsien Hsieh Shun-Fa Yang Horng-Rong Chang Ko-Hsiu Lu Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway Molecules erk metastasis osteosarcoma ps-1 tomatidine |
| title | Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway |
| title_full | Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway |
| title_fullStr | Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway |
| title_full_unstemmed | Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway |
| title_short | Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway |
| title_sort | tomatidine represses invasion and migration of human osteosarcoma u2os and hos cells by suppression of presenilin 1 and c raf mek erk pathway |
| topic | erk metastasis osteosarcoma ps-1 tomatidine |
| url | https://www.mdpi.com/1420-3049/25/2/326 |
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