Calcium efflux from the endoplasmic reticulum regulates cisplatin-induced apoptosis in human cervical cancer HeLa cells

Shen,Luyan; Wen,Naiyan; Xia,Meihui; Zhang,Yu; Liu,Weimin; Xu,Ye; Sun,Liankun

doi:10.3892/ol.2016.4278

Calcium efflux from the endoplasmic reticulum regulates cisplatin-induced apoptosis in human cervical cancer HeLa cells

Authors:
- Luyan Shen
- Naiyan Wen
- Meihui Xia
- Yu Zhang
- Weimin Liu
- Ye Xu
- Liankun Sun
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Affiliations: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Obstetrics and Gynecology, First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Interventional Radiology, Renmin Hospital, Jilin, Jilin 132013, P.R. China, Medical Research Laboratory, Jilin Medical College, Jilin, Jilin 132013, P.R. China
Published online on: February 25, 2016 https://doi.org/10.3892/ol.2016.4278
Pages: 2411-2419
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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