DMS triggers apoptosis associated with the inhibition of SPHK1/NF-κB activation and increase in intracellular Ca2+ concentration in human cancer cells

Chen,Kan; Pan,Qiuwei; Gao,Ying; Yang,Xinyan; Wang,Shibing; Peppelenbosch,Maikel   P.; Kong,Xiangdong

doi:10.3892/ijmm.2013.1541

DMS triggers apoptosis associated with the inhibition of SPHK1/NF-κB activation and increase in intracellular Ca2+ concentration in human cancer cells

Authors:
- Kan Chen
- Qiuwei Pan
- Ying Gao
- Xinyan Yang
- Shibing Wang
- Maikel P. Peppelenbosch
- Xiangdong Kong
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Affiliations: Bio-X Center, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P.R. China, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, 3000 CA, The Netherlands, Department of Radiotherapy Oncology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: October 30, 2013 https://doi.org/10.3892/ijmm.2013.1541
Pages: 17-24
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

N,N-Dimethyl-D-erythro-sphingosine (DMS) is known to induce cell apoptosis by specifically inhibiting sphingosine kinase 1 (SPHK1) and modulating the activity of cellular ceramide levels. The present study investigated the effects and the mechanism(s) of action of DMS in human lung cancer cells. We found that DMS dose-dependently suppressed cell proliferation and induced cell apoptosis in the human lung cancer cell line, A549. Mechanistically, treatment with DMS suppressed the activation of SPHK1 and nuclear factor-κB (NF-κB) p65, but increased intracellular [Ca2+]i in A549 cells. This study demonstrates that DMS triggers the apoptosis of human lung cancer cells through the modulation of SPHK1, NF-κB and calcium signaling. These molecules may represent targets for anticancer drug design.

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