Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells

Abstract

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.

Autophagy and Hallmarks of Cancer

“…78 TFEB nuclear translocation upregulates autophagy-related regulators, including ATP6V0D1 , LAMP1 , CTSB , MAP1LC3B , and UVRAG. 79 Of note, emerging studies have demonstrated that TFEB serves as a bridge to mediate upstream regulators and autophagy progression in cancer cells. STUB1 regulates autophagy and mitochondrial biogenesis by modulating TFEB activity.…”

Suppressing ROS‐TFE3‐dependent autophagy enhances ivermectin‐induced apoptosis in human melanoma cells

“…However, the mechanism that underlies the ivermectin‐mediated enhancement of TFE3 activity and nuclear translocation remains elusive. Recent studies have linked the accumulation of ROS to TFEB activation in the invasion and migration of cancer . TFE3 and TFEB share a similar structure that includes three critically important regions, and these two factors bind overlapping sets of promoters and are post‐transcriptionally regulated through a similar mechanism .…”

Cistanche tubulosa phenylethanoid glycosides induce apoptosis in Eca‑109 cells via the mitochondria‑dependent pathway

“…Similarly, the free radical scavenging activity was observed in the present study. Therefore, it was speculated that some components, including verbascoside, iso-verbascoside and salidroside in a high dose of CTPG-W might immediately induce ROS generation to cause apoptosis of Eca-109 cells (41,42), and then ROS was scavenged by echinacoside. Another possible reason for the differences in ROS production by CTPG and CTPG-W is that different cell lines were used in this study and previous study (24).…”