Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells

The function of autophagy in cisplatin-treated cancer cells is not fully understood. Cisplatin treatment induced degradation of ubiquitinated proteins by autophagy, which reduced apoptosis induced by endoplasmic reticulum (ER) stress and downregulated the mitochondrial pathway of apoptosis. Inhibiti...

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Bibliographic Details
Published in:Cancer letters 2012-01, Vol.314 (2), p.232-243
Main Authors: Xu, Ye, Yu, Huimei, Qin, Hanjiao, Kang, JinSong, Yu, Chunyan, Zhong, Jiateng, Su, Jing, Li, HongYan, Sun, LianKun
Format: Article
Language:English
Subjects:
Adenine - analogs & derivatives
Adenine - pharmacology
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis Regulatory Proteins - physiology
Autophagy
Autophagy - drug effects
Beclin-1
Cancer therapies
Cell Proliferation - drug effects
Cervical cancer
Chemotherapy
chloroquine
Chloroquine - pharmacology
Cisplatin
Cisplatin - pharmacology
Cytotoxicity
Deoxyribonucleic acid
DNA
Endoplasmic reticulum
Endoplasmic Reticulum Stress - drug effects
Endoribonucleases - physiology
ER stress
Female
HeLa Cells
Hematology, Oncology and Palliative Medicine
Homeostasis
Humans
Hypotheses
MAP Kinase Signaling System
Membrane Proteins - physiology
Microscopy
Protein folding
Protein-Serine-Threonine Kinases - physiology
proteins
Studies
tunicamycin
Tunicamycin - pharmacology
uterine cervical neoplasms
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - pathology
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Summary:The function of autophagy in cisplatin-treated cancer cells is not fully understood. Cisplatin treatment induced degradation of ubiquitinated proteins by autophagy, which reduced apoptosis induced by endoplasmic reticulum (ER) stress and downregulated the mitochondrial pathway of apoptosis. Inhibition of autophagy using 3-methyladenine (3-MA) or chloroquine (CQ) increased the levels of intracellular misfolded proteins, which enhanced cellular apoptosis. We found that tunicamycin, an ER stress inducer, augmented cisplatin cytotoxicity by upregulating ER stress-mediated apoptosis. Our data indicates that autophagy plays an important role in preventing cisplatin-induced apoptosis in HeLa cells, thus inhibition of autophagy may improve cisplatin chemotherapy.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.09.034