Alantolactone induces apoptosis and improves chemosensitivity of pancreatic cancer cells by impairment of autophagy-lysosome pathway via targeting TFEB.
He, Ruizhi; Shi, Xiuhui; Zhou, Minet al.
2018 • In Toxicology and Applied Pharmacology, 356, p. 159 - 171
[en] The lysosome is emerging as a central regulator of the autophagic process, which plays a critical role in tumor growth and chemoresistance. Alantolactone, which is a natural compound produced by Inula helenium, has been shown to induce apoptosis in numerous cancer types. However, the mechanism by which alantolactone regulates apoptosis is still poorly understood. In this work, we observed that alantolactone caused the accumulation of autophagosomes due to impaired autophagic degradation and substantially inhibited the activity and expression of CTSB/CTSD proteins that when depleted caused lysosomal dysfunction. Furthermore, we found that alantolactone inhibited the proliferation of pancreatic cancer cells in vitro and in vivo and enhanced the chemosensitivity of pancreatic cancer cells to oxaliplatin. In addition, a reduction in TFEB levels was a critical event in the apoptosis and cell death caused by alantolactone. Our data demonstrated that alantolactone, which impaired autophagic degradation, was a pharmacological inhibitor of autophagy in pancreatic cancer cells and markedly enhanced the chemosensitivity of pancreatic cancer cells to oxaliplatin.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
He, Ruizhi ; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Shi, Xiuhui ; Université de Liège - ULiège > Département de pharmacie ; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Zhou, Min; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Zhao, Yan; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Pan, Shutao; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Zhao, Chunle; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Guo, Xingjun; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Wang, Min; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Li, Xu; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: kuai_1985@hotmail.com
Qin, Renyi; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: ryqin@tjh.tjmu.edu.cn
Language :
English
Title :
Alantolactone induces apoptosis and improves chemosensitivity of pancreatic cancer cells by impairment of autophagy-lysosome pathway via targeting TFEB.
NSCF - National Natural Science Foundation of China
Funding text :
This study was supported by the National Natural Science Foundation of China (No. 81502633 to Xu Li, No. 81773160 to Min Wang, No. 81772950 to Renyi Qin).
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