Magnesium, the second most predominant intracellular
cation, plays a crucial role in many physiological functions;
magnesium-based
biomaterials have been widely used in clinical application. In a variety of
cancer types, the high intracellular concentration of
magnesium contributes to
cancer initiation and progression. Therefore, we initiated this study to investigate the likelihood of confounding
magnesium with
cancer therapy. In this study, the anti-
tumor activity of
magnesium and underlying mechanisms were assessed in
bladder cancer both in vitro and in vivo. The results indicated that the proliferation of
bladder cancer cells was inhibited by treatment with a high concentration of
MgCl2 or MgSO4. The apoptosis, G0/G1 cell cycle arrest, autophagy, and ER stress were promoted following treatment with
MgCl2. However, the migratory ability of
MgCl2 treated cells was similar to that of control cells, as revealed by the trans-well assay. Besides, no significant difference was observed in the proportion of CD44 or CD133 positive cells between the control and
MgCl2 treated cells. Thus, to improve the
therapeutic effect of
magnesium, VPA was used to treat
cancer cells in combination with
MgCl2. As expected, combination treatment with
MgCl2 and VPA could markedly reduce proliferation, migration, and in vivo tumorigenicity of UC3 cells. Moreover, the Wnt signaling was down-regulated, and ERK signaling was activated in the cells treated with combination treatment. In conclusion, the accurate utilization of
MgCl2 in targeting autophagy might be beneficial in
cancer therapy. Although further studies are warranted, the combination treatment of
MgCl2 with VPA is an effective strategy to improve the outcome of
chemotherapy.