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...Continue Reading
References
Dihydroartemisinin exhibits antitumor activity toward hepatocellular carcinoma in vitro and in vivo.
Citations
ClC-3 promotes paclitaxel resistance via modulating tubulins polymerization in ovarian cancer cells.
Related Concepts
Related Feeds
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis