Ethanol Promotes Cell Migration via Activation of Chloride Channels in Nasopharyngeal Carcinoma Cells

Abstract

Background: Excessive alcohol consumption has been identified as a significant risk factor for cancer development. Chloride channels have been proved previously by us and others to be involved in cancer cell migration. However, it is unknown whether chloride channels are associated with the effects of ethanol (EtOH) on cancer cell activities.

Methods: The effects of EtOH on migration were detected by the wound healing assay in the nasopharyngeal carcinoma cells (CNE-2Z) and the normal nasopharyngeal epithelial cells (NP69-SV40T). The whole-cell patch clamp technique was used to record the EtOH-induced chloride current. The characteristics of the current were studied by anion substitution, hypertonic challenges, and channel blockers.

Results: EtOH promoted the migration of cancerous CNE-2Z cells, but could hardly affect the migration of normal NP69-SV40T cells. The EtOH-induced migration could be inhibited by the chloride channel blockers, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen. The exposure of CNE-2Z cells to EtOH activated a chloride current, with the ion selectivity of I(-) >Br(-) > Cl(-) >gluconate, demonstrated by ion substitution experiments. EtOH could still activate a similar chloride current in the absence of Ca(2+) in the medium. The current could be inhibited by the hypertonicity-induced cell shrinkage and the channel blockers NPPB and tamoxifen. EtOH could also activate a chloride current in normal NP69-SV40T cells, with the properties similar to those in CNE-2Z cells, but the current density was much smaller than that recorded in cancerous CNE-2Z cells.

Conclusions: It has been demonstrated in this study that EtOH can activate chloride channels and promote cell migration in cancerous cells, but can hardly affect the activities in normal cells. The data suggest for the first time that EtOH may promote cell migration via activation of chloride channels; long-term exposure to EtOH may increase the incident of tumor metastasis.

Keywords: Cell Migration; Chloride Channels; Ethanol; Patch Clamp Techniques.