Opening of the CLC-3 chloride channel induced by dihydroartemisinin contributed to early apoptotic events in human poorly differentiated nasopharyngeal carcinoma cells.

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: Congran Zhou, Xinwei Tang, Jingkui Xu, Jiajia Wang, Yaping Yang, Yehui Chen, Lixin Chen, Liwei Wang, Linyan Zhu, Haifeng Yang
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 119 Issue 11 Pg. 9560-9572 (11 2018) ISSN: 1097-4644 [Electronic] United States
• PMID: 30171707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Artemisinins
• Chloride Channels
• ClC-3 channel
• RNA, Small Interfering
• artenimol

Topics

• Apoptosis (drug effects)
• Artemisinins (therapeutic use)
• Blotting, Western
• Cell Line
• Cell Survival (drug effects)
• Chloride Channels (metabolism)
• Flow Cytometry
• Humans
• Nasopharyngeal Carcinoma (drug therapy, metabolism)
• RNA, Small Interfering