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Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells
Background/Aims:
Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear.
Methods:
We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy.
Results:
We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy.
Conclusions:
These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells.
Insights
Salidroside induces human chondrosarcoma cell death by activating ROS-dependent autophagy. Blocking this autophagy enhances salidroside
Area of Science:
- Oncology
- Cell Biology
- Molecular Mechanisms
Background:
- Autophagy modulation is a potential therapeutic strategy for chondrosarcoma.
- Salidroside shows anti-carcinogenic activity, but its role in chondrosarcoma cell death and autophagy is unclear.
Purpose of the Study:
- To investigate salidroside's effect on autophagy and cell death in human chondrosarcoma.
- To elucidate the role of TFEB-dependent autophagy and ROS signaling in salidroside's anti-cancer activity.
Main Methods:
- Human chondrosarcoma SW1353 cells were treated with salidroside.
- Evaluated autophagy markers (LC3-II, P62), apoptosis, TFEB activation, and reactive oxygen species (ROS) generation.
- Utilized RT-PCR, Western-blotting, immunofluorescence, and reporter assays.
Main Results:
- Salidroside induced apoptosis and autophagy in SW1353 cells.
- Autophagy played a cytoprotective role, as blocking it enhanced salidroside-induced apoptosis.
- Salidroside activated TFEB-dependent autophagy via ROS generation, which was abrogated by a ROS scavenger (NAC).
Conclusions:
- Salidroside enhances TFEB-dependent autophagy through ROS signaling in chondrosarcoma cells.
- Targeting ROS-TFEB-dependent autophagy may improve salidroside's efficacy against human chondrosarcoma.