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Opening of the CLC-3 chloride channel induced by dihydroartemisinin contributed to early apoptotic events in human poorly differentiated nasopharyngeal carcinoma cells.
J Cell Biochem 2018; 119(11):9560-9572JC

Abstract

Nasopharyngeal carcinoma (NPC) is a specific type of head and neck cancer that is prevalent in Southeast Asia. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has specific anticancer activity. Here, we aimed to investigate the role of the CLC-3 chloride channel in the anticancer effect of DHA in poorly differentiated NPC CNE-2Z cells. First, we observed that DHA could specifically inhibit the proliferation, induce apoptosis, and increase cleaved caspase-3 expression in the CNE-2Z cells. Then, we found that DHA could activate chloride channels, which led to Cl- efflux and apoptotic volume decrease (AVD) in the early stage in the CNE-2Z cells. DHA also specifically increased CLC-3 chloride channel protein expression in the CNE-2Z cells. Silencing of the CLC-3 protein expression depleted the Cl- currents, and decreased the AVD capacity and cell apoptosis induced by DHA. Finally, we revealed that the [Ca2+ ]i increased after around 6 hours of treatment with DHA, which was also inhibited by silencing of the CLC-3 protein expression. Our data demonstrated that the selective antitumor activities of DHA in NPC may occur through the specific activation of the CLC-3 Cl- channel, leading to Cl- efflux, and induced AVD, then led to [Ca2+ ]i accumulation and caspase-3 activation, and finally induced apoptosis. The activation of the CLC-3 chloride channel played an essential and proximal upstream role in the antitumor activities of DHA.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.Analysis and Test Center, Jinan University, Guangzhou, China.Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30171707

Citation

Zhou, Congran, et al. "Opening of the CLC-3 Chloride Channel Induced By Dihydroartemisinin Contributed to Early Apoptotic Events in Human Poorly Differentiated Nasopharyngeal Carcinoma Cells." Journal of Cellular Biochemistry, vol. 119, no. 11, 2018, pp. 9560-9572.
Zhou C, Tang X, Xu J, et al. Opening of the CLC-3 chloride channel induced by dihydroartemisinin contributed to early apoptotic events in human poorly differentiated nasopharyngeal carcinoma cells. J Cell Biochem. 2018;119(11):9560-9572.
Zhou, C., Tang, X., Xu, J., Wang, J., Yang, Y., Chen, Y., ... Yang, H. (2018). Opening of the CLC-3 chloride channel induced by dihydroartemisinin contributed to early apoptotic events in human poorly differentiated nasopharyngeal carcinoma cells. Journal of Cellular Biochemistry, 119(11), pp. 9560-9572. doi:10.1002/jcb.27274.
Zhou C, et al. Opening of the CLC-3 Chloride Channel Induced By Dihydroartemisinin Contributed to Early Apoptotic Events in Human Poorly Differentiated Nasopharyngeal Carcinoma Cells. J Cell Biochem. 2018;119(11):9560-9572. PubMed PMID: 30171707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opening of the CLC-3 chloride channel induced by dihydroartemisinin contributed to early apoptotic events in human poorly differentiated nasopharyngeal carcinoma cells. AU - Zhou,Congran, AU - Tang,Xinwei, AU - Xu,Jingkui, AU - Wang,Jiajia, AU - Yang,Yaping, AU - Chen,Yehui, AU - Chen,Lixin, AU - Wang,Liwei, AU - Zhu,Linyan, AU - Yang,Haifeng, Y1 - 2018/09/01/ PY - 2018/02/28/received PY - 2018/06/26/accepted PY - 2018/9/2/pubmed PY - 2019/10/11/medline PY - 2018/9/2/entrez KW - CLC-3 chloride channel KW - apoptosis KW - dihydroartemisinin KW - nasopharyngeal carcinoma SP - 9560 EP - 9572 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 119 IS - 11 N2 - Nasopharyngeal carcinoma (NPC) is a specific type of head and neck cancer that is prevalent in Southeast Asia. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has specific anticancer activity. Here, we aimed to investigate the role of the CLC-3 chloride channel in the anticancer effect of DHA in poorly differentiated NPC CNE-2Z cells. First, we observed that DHA could specifically inhibit the proliferation, induce apoptosis, and increase cleaved caspase-3 expression in the CNE-2Z cells. Then, we found that DHA could activate chloride channels, which led to Cl- efflux and apoptotic volume decrease (AVD) in the early stage in the CNE-2Z cells. DHA also specifically increased CLC-3 chloride channel protein expression in the CNE-2Z cells. Silencing of the CLC-3 protein expression depleted the Cl- currents, and decreased the AVD capacity and cell apoptosis induced by DHA. Finally, we revealed that the [Ca2+ ]i increased after around 6 hours of treatment with DHA, which was also inhibited by silencing of the CLC-3 protein expression. Our data demonstrated that the selective antitumor activities of DHA in NPC may occur through the specific activation of the CLC-3 Cl- channel, leading to Cl- efflux, and induced AVD, then led to [Ca2+ ]i accumulation and caspase-3 activation, and finally induced apoptosis. The activation of the CLC-3 chloride channel played an essential and proximal upstream role in the antitumor activities of DHA. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/30171707/Opening_of_the_CLC_3_chloride_channel_induced_by_dihydroartemisinin_contributed_to_early_apoptotic_events_in_human_poorly_differentiated_nasopharyngeal_carcinoma_cells_ L2 - https://doi.org/10.1002/jcb.27274 DB - PRIME DP - Unbound Medicine ER -