title: Inhibition of store-operated Ca2+entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate.
abstract: Sodium butyrate (NaBu), a histone deacetylase inhibitor, has demonstrated anti-tumor effects in several cancers, and is a promising candidate chemotherapeutic agent. However, its roles in nasopharyngeal carcinoma (NPC), an endemic malignant disease in Southern China and Southeast Asia, has rarely been studied. In the present study, MTT assay, colony formation assay, flow cytometry analysis and western blotting were performed to explore the influence of NaBu on NPC cells and its underlying mechanism. NaBu induced morphological changes and inhibited proliferation in 5-8F and 6-10B cells. MTT assay revealed that NaBu was cytotoxic to 5-8F and 6-10B cells in a dose- and time-dependent manner. Furthermore, flow cytometry analysis revealed that NaBu induced obvious cell apoptosis in 5-8F and 6-10B cells due to the activation of the mitochondrial apoptosis axis. In addition, flow cytometry analysis and western blotting demonstrated that NaBu could enhance the Ca2+influx by promoting store-operated Ca2+entry (SOCE) in 5-8F and 6-10B cells. Inhibition of SOCE by specific inhibitors or downregulated expression of calcium release-activated calcium channel protein 1 and stromal interaction molecule 1 could counteract the apoptosis of NPC cells induced by NaBu. Thus, the current study revealed that enhanced SOCE and activated mitochondrial apoptosis axis may account for the mechanisms of cytotoxicity of NaBu in NPC cells, and that NaBu serves as a promising chemotherapeutic agent in NPC therapy.
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China; Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Ren
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Guoling
authors.initials: G
authors.lastname: Huang
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Feng
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xingjun
authors.initials: X
authors.lastname: Jiang
keywords: SOCE; mitochondrial apoptosis; nasopharyngeal carcinoma; sodium butyrate