Lithium chloride inhibits cell survival, overcomes drug resistance, and triggers apoptosis in multiple myeloma via activation of the Wnt/β-catenin pathway.

Multiple myeloma (MM) is an extremely malignant plasma cell disease, which is still incurable due to its drug resistance. Lithium chloride (LiCl) functions in many pathological processes, including bipolar disorder, acute brain injuries, and chronic neurodegenerative diseases, but its antagonistic role in MM progression has not been reported thus far. In this study, we found that LiCl inhibited MM cell proliferation and induced MM cell cycle G2/M phase arrest in a dose-dependent manner. Moreover, LiCl overcomes bortezomib (BTZ)-mediated resistance in MM cells and induces apoptosis in BTZ-resistant cells. Our data preliminarily indicate that LiCl induces MM cell apoptosis via activating the Wnt/β-catenin signaling pathway. Overall, our results define LiCl as an inducer of MM cell apoptosis and unveil a crosstalk between BTZ and LiCl in facilitating cell apoptosis.