Inactivation of CACNA1H induces cell apoptosis by initiating endoplasmic reticulum stress in glioma.

Abstract

Background: Ca²⁺ channels are abnormally expressed in various tumor cells and are involved in the progression of human glioma. Here, we explored the role of a calcium channel, voltage-dependent, T-type, alpha 1H subunit (CACNA1H), which encodes T-type Ca²⁺ channel Cav3.2 in glioma cells.

Methods: Cell viability and apoptosis were detected using cell-counting kit-8 and flow cytometry, respectively. The expression of target protein was determined using western blot analysis.

Results: Cell viability of U251 cells was inhibited significantly after the knockdown of CACNA1H. The apoptosis of U251 cells was enhanced significantly after the knockdown of CACNA1H. Importantly, knockdown of CACNA1H decreased the levels of p-PERK, GRP78, CHOP, and ATF6, indicating that CACNA1H knockdown activated endoplasmic reticulum stress (ERS) in U251 cells. In addition, T-type Ca²⁺ channel inhibitor NNC55-0396 also induced apoptosis through the activation of ERS in U251 cells. ERS inhibitor UR906 could block CACNA1H inhibitor ABT-639-induced apoptosis.

Conclusion: Suppression of CACNA1H activated the ERS and thus induced apoptosis in glioma cells. T-type Ca²⁺ channel inhibitors ABT-639 and NNC55-0396 also induced apoptosis through ERS in glioma cells. Our data highlighted the effect of CACNA1H as an oncogenic gene in human glioma.