title: Calcium efflux from the endoplasmic reticulum regulates cisplatin-induced apoptosis in human cervical cancer HeLa cells.
abstract: The function of calcium efflux from the endoplasmic reticulum (ER) in cisplatin-induced apoptosis is not fully understood in cancer cells. The present study used western blot analysis, flow cytometry, immunofluorescence and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay to investigate calcium signaling in human cervical cancer cells exposed to cisplatin. In the present study, treatment with cisplatin increased free Ca2+levels in the cytoplasm and mitochondria of human cervical cancer HeLa cells, which further triggers the mitochondria-mediated and ER stress-associated apoptosis pathways. Notably, blocking calcium signaling using the calcium chelating agent bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethyl ester inhibited cisplatin-induced apoptosis via downregulation of the calcium-dependent proteases, the calpains, and innate apoptosis proteins, such as caspsae-3, caspase-4 and C/EBP homologous protein (CHOP). In addition, use of the inositol triphosphate receptor inhibitor, 2-aminoethyl diphenylborinate, to inhibit calcium efflux from the ER resulted in similar effects. This data indicated that calcium efflux from the ER plays a significant role in cisplatin-induced apoptosis in human cervical cancer HeLa cells, which provides further mechanistic insights into the tumor cell-killing effect of cisplatin and potential therapeutic strategies to improve cisplatin chemotherapy.
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China; Department of Obstetrics and Gynecology, Second Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Luyan
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Naiyan
authors.initials: N
authors.lastname: Wen
authors.affiliation: Department of Obstetrics and Gynecology, First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Meihui
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Zhang
authors.affiliation: Department of Interventional Radiology, Renmin Hospital, Jilin, Jilin 132013, P.R. China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Medical Research Laboratory, Jilin Medical College, Jilin, Jilin 132013, P.R. China.
authors.forename: Y E
authors.initials: YE
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Liankun
authors.initials: L
authors.lastname: Sun
keywords: apoptosis; calcium; cervical cancer; cisplatin; endoplasmic reticulum stress