Artocarpin induces cell apoptosis in human osteosarcoma cells through endoplasmic reticulum stress and reactive oxygen species

2018 ◽  
Vol 234 (8) ◽  
pp. 13157-13168 ◽  
Author(s):  
Chiang‐Wen Lee ◽  
Miao‐Ching Chi ◽  
Tsung‐Ming Chang ◽  
Ju‐Fang Liu
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

scholarly journals Sestrin2-Mediated Autophagy Contributes to Drug Resistance via Endoplasmic Reticulum Stress in Human Osteosarcoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Tang ◽  
Xinghui Wei ◽  
Tian Li ◽  
Wei Wang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Tumour Progression ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Gene Target ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.

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