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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
Author(s) -
Zhou Congran,
Tang Xinwei,
Xu Jingkui,
Wang Jiajia,
Yang Yaping,
Chen Yehui,
Chen Lixin,
Wang Liwei,
Zhu Linyan,
Yang Haifeng
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27274
Subject(s) - dihydroartemisinin , chloride channel , apoptosis , nasopharyngeal carcinoma , chemistry , gene silencing , efflux , cancer research , channel blocker , microbiology and biotechnology , biochemistry , biology , medicine , artemisinin , immunology , gene , plasmodium falciparum , organic chemistry , malaria , calcium , radiation therapy
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 [Ca 2+ ] 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 [Ca 2+ ] 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.