Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis
Protodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of huma...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/3/395 |
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| author | Chien-Feng Huang Yi-Hsien Hsieh Shun-Fa Yang Chao-Hung Kuo Pei-Han Wang Chung-Jung Liu Renn-Chia Lin |
| author_facet | Chien-Feng Huang Yi-Hsien Hsieh Shun-Fa Yang Chao-Hung Kuo Pei-Han Wang Chung-Jung Liu Renn-Chia Lin |
| author_sort | Chien-Feng Huang |
| collection | DOAJ |
| description | Protodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of human HOS and 143B OS cells through the upregulation of apoptotic-related proteins (cleaved caspase-3, cleaved caspase-9, and cleaved PARP) and mitophagy-related proteins (LC3B and NIX), which contribute to the induction of apoptosis, and MMP (mitochondrial membrane potential) dysfunction and mitophagy. The inhibition of LC3 or NIX was shown to decrease apoptosis and mitophagy in PD-treated OS cells. The knockdown of p38MAPK by siRNA decreased mitochondrial dysfunction, autophagy, mitophagy, and the NIX/LC3B expression in the PD-treated OS cells. A binding affinity analysis revealed that the smaller the KD value (−7.6 Kcal/mol and −8.9 Kcal/mol, respectively), the greater the binding affinity in the PD-NIX and PD-LC3 complexes. These findings show the inhibitory effects of PD-induced mitophagy in human OS cells and may represent a novel therapeutic strategy for human OS, by targeting the NIX/LC3 pathways. |
| first_indexed | 2024-03-11T09:48:48Z |
| format | Article |
| id | doaj.art-1e0f82c22b384a388319cc6e439735c7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:48:48Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-1e0f82c22b384a388319cc6e439735c72023-11-16T16:21:01ZengMDPI AGCells2073-44092023-01-0112339510.3390/cells12030395Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 AxisChien-Feng Huang0Yi-Hsien Hsieh1Shun-Fa Yang2Chao-Hung Kuo3Pei-Han Wang4Chung-Jung Liu5Renn-Chia Lin6Department of Critical Care Medicine, Tungs’ Taichung MetroHarbor Hospital, Taichung City 435403, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung City 40201, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung City 40201, TaiwanDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung City 40201, TaiwanDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, TaiwanDepartment of Orthopedics, Chung Shan Medical University Hospital, Taichung City 40201, TaiwanProtodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of human HOS and 143B OS cells through the upregulation of apoptotic-related proteins (cleaved caspase-3, cleaved caspase-9, and cleaved PARP) and mitophagy-related proteins (LC3B and NIX), which contribute to the induction of apoptosis, and MMP (mitochondrial membrane potential) dysfunction and mitophagy. The inhibition of LC3 or NIX was shown to decrease apoptosis and mitophagy in PD-treated OS cells. The knockdown of p38MAPK by siRNA decreased mitochondrial dysfunction, autophagy, mitophagy, and the NIX/LC3B expression in the PD-treated OS cells. A binding affinity analysis revealed that the smaller the KD value (−7.6 Kcal/mol and −8.9 Kcal/mol, respectively), the greater the binding affinity in the PD-NIX and PD-LC3 complexes. These findings show the inhibitory effects of PD-induced mitophagy in human OS cells and may represent a novel therapeutic strategy for human OS, by targeting the NIX/LC3 pathways.https://www.mdpi.com/2073-4409/12/3/395protodioscinhuman osteosarcoma cellapoptosisp38MAPKmitophagyNIX |
| spellingShingle | Chien-Feng Huang Yi-Hsien Hsieh Shun-Fa Yang Chao-Hung Kuo Pei-Han Wang Chung-Jung Liu Renn-Chia Lin Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis Cells protodioscin human osteosarcoma cell apoptosis p38MAPK mitophagy NIX |
| title | Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis |
| title_full | Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis |
| title_fullStr | Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis |
| title_full_unstemmed | Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis |
| title_short | Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis |
| title_sort | mitophagy effects of protodioscin on human osteosarcoma cells by inhibition of p38mapk targeting nix lc3 axis |
| topic | protodioscin human osteosarcoma cell apoptosis p38MAPK mitophagy NIX |
| url | https://www.mdpi.com/2073-4409/12/3/395 |
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