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. 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.
Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Ye
Y
Xu
Huimei
H
Yu
Hanjiao
H
Qin
JinSong
J
Kang
Chunyan
C
Yu
Jiateng
J
Zhong
Jing
J
Su
HongYan
H
Li
LianKun
L
Sun
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000502:physiology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D014415:Tunicamycin / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D014415:Tunicamycin; C025946:3-methyladenine; D002738:Chloroquine; C403982:ERN2 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D000225:Adenine; D002945:Cisplatin